Publications by authors named "Cláudio Da Cunha"

92 Publications

Allopregnanolone Decreases Evoked Dopamine Release Differently in Rats by Sex and Estrous Stage.

Front Pharmacol 2020 14;11:608887. Epub 2021 Jan 14.

Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, United States.

Mesolimbic dopamine transmission is dysregulated in multiple psychiatric disorders, including addiction. Previous studies found that the endogenous GABAergic steroid (3α,5α)-3-hydroxy-5-pregnan-20-one (allopregnanolone) modulates dopamine levels in the nucleus accumbens and prefrontal cortex. As allopregnanolone is a potent positive allosteric modulator of GABA receptors, and GABA receptors can regulate dopamine release, we hypothesized that allopregnanolone would reduce phasic fluctuations in mesolimbic dopamine release that are important in learning and reward processing. We used fast-scan cyclic voltammetry in anesthetized female and male rats to measure dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area, before and after administration of allopregnanolone. Allopregnanolone (7.5-25 mg/kg, IP) reduced evoked dopamine release in both male and female rats, compared to β-cyclodextrin vehicle. In males, all doses of allopregnanolone decreased dopamine transmission, with stronger effects at 15 and 25 mg/kg allopregnanolone. In females, 15 and 25 mg/kg allopregnanolone reduced dopamine release, while 7.5 mg/kg allopregnanolone was no different from vehicle. Since allopregnanolone is derived from progesterone, we hypothesized that high endogenous progesterone levels would result in lower sensitivity to allopregnanolone. Consistent with this, females in proestrus (high progesterone levels) were less responsive to allopregnanolone than females in other estrous cycle stages. Furthermore, 30 mg/kg progesterone reduced evoked dopamine release in males, similar to allopregnanolone. Our findings confirm that allopregnanolone reduces evoked dopamine release in both male and female rats. Moreover, sex and the estrous cycle modulated this effect of allopregnanolone. These results extend our knowledge about the pharmacological effects of neurosteroids on dopamine transmission, which may contribute to their therapeutic effects.
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http://dx.doi.org/10.3389/fphar.2020.608887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840599PMC
January 2021

Does the anthropometric profile influence infection morbidity after coronary artery bypass grafting?

J Card Surg 2021 Apr 19;36(4):1194-1200. Epub 2021 Jan 19.

Department of Cardiovascular Surgery, Instituto de Cardiologia do Distrito Federal, Brasilia, Distrito Federal, Brazil.

Background: Infection after cardiovascular surgery is multifactorial. We sought to determine whether the anthropometric profile influences the occurrence of infection after isolated coronary artery bypass grafting (CABG).

Methods: Between January 2011 and June 2016, 1777 consecutive adult patients were submitted to isolated coronary artery bypass grafting. Mean age was 61.7 ± 9.8 years and 1193 (67.1%) were males. Patients were divided into four groups according to the body mass index (BMI) classification: underweight (BMI < 18.5 kg/m ; N = 17, 0.9%), normal range (BMI: 18.5-24.99 kg/m ; N = 522, 29.4%), overweight (BMI: 25-29.99 kg/m ; N = 796, 44.8%), and obese (BMI > 30 kg/m ; N = 430, 24.2%). In-hospital outcomes were compared and independent predictors of infection were obtained through multiple Poisson regression with a robust variation.

Results: Independent predictors of any infection morbidity were female sex (relative ratio [RR], 1.47; p = .002), age > 60 years (RR, 1.85; p < .0001), cardiopulmonary bypass > 120 min (RR, 1.89; p = .0007), preoperative myocardial infarction < 30 days (RR, 1.37; p = .01), diabetes mellitus (RR, 1.59; p = .0003), ejection fraction < 48% (RR, 2.12; p < .0001), and blood transfusion (RR, 1.55; p = .0008). Among other variables, obesity, as well as diabetes mellitus, were independent predictors of superficial and deep sternal wound infection.

Conclusions: Other factors rather than the anthropometric profile are more important in determining the occurrence of any infection after CABG. However, surgical site infection has occurred more frequently in obese patients. Appropriate patient selection, control of modifiable factors, and application of surgical bundles would minimize this important complication.
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http://dx.doi.org/10.1111/jocs.15334DOI Listing
April 2021

Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson's disease.

Brain Res Bull 2021 Mar 31;168:63-73. Epub 2020 Dec 31.

Department of Pharmacology, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, C.P. 19031, 81531-980, Curitiba, PR, Brazil. Electronic address:

The most common features of Parkinson's disease (PD) are motor impairments, but many patients also present depression and memory impairment. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to be effective in patients with treatment-resistant major depression. Thus, the present study evaluated the action of ketamine on memory impairment and depressive-like behavior in an animal model of PD. Male Wistar rats received a bilateral infusion of 6 μg/side 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). Short-term memory was evaluated by the social recognition test, and depressive-like behaviors were evaluated by the sucrose preference and forced swimming tests (FST). Drug treatments included vehicle (i.p., once a week); ketamine (5, 10 and 15 mg/kg, i.p., once a week); and imipramine (20 mg/kg, i.p., daily). The treatments were administered 21 days after the SNc lesion and lasted for 28 days. The SNc lesion impaired short-term social memory, and all ketamine doses reversed the memory impairment and anhedonia (reduction of sucrose preference) induced by 6-OHDA. In the FST, 6-OHDA increased immobility, and all doses of ketamine and imipramine reversed this effect. The anti-immobility effect of ketamine was associated with an increase in swimming but not in climbing, suggesting a serotonergic effect. Ketamine and imipramine did not reverse the 6-OHDA-induced reduction in tyrosine hydroxylase immunohistochemistry in the SNc. In conclusion, ketamine reversed depressive-like behaviors and short-term memory impairment in rats with SNc bilateral lesions, indicating a promising profile for its use in PD patients.
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http://dx.doi.org/10.1016/j.brainresbull.2020.12.011DOI Listing
March 2021

Evidence that haloperidol impairs learning and motivation scores in a probabilistic task by reducing the reward expectation.

Behav Brain Res 2020 10 15;395:112858. Epub 2020 Aug 15.

Universidade Federal do Paraná (UFPR) - Departamento de Farmacologia, 81531- 980, Curitiba, Brazil. Electronic address:

Activation of midbrain dopamine neurons in response to positive prediction errors and reward predictive cues is proposed to "energize" reward seeking behaviors and approach responses to places where the reward is expected. In the present study, we tested the effect of the D2-dopamine receptor antagonist haloperidol on response latencies to enter two arms of a Y-maze with different reward probabilities. Adult male Wistar rats were trained to explore the Y-maze with sucrose pellets placed 30% of times at the end of one arm and 70% of times at the opposite arm. Therefore, the reward expectation was different among arms, and was updated in the trials when the reward was omitted. After training, rats received 0.05, 0.10, 0.15 mg/kg haloperidol, or saline 30 min before the test session. In the last, but not in the first trials, haloperidol caused a dose-dependent increase in arm choice latency and response latency. Saline, but not haloperidol, treated rats presented significantly longer response latencies for the 30% compared to the 70% reward probability arm. Haloperidol also caused a dose-dependent decrease in the number of entries in the 70% reward probability arm, increased the number of non-responses, and caused a dose-dependent increase in the number of re-entries in the 30% reward probability arm after non-rewarded trials. Control experiments suggested that haloperidol did not cause motor impairment or satiation, but rather impaired learning and motivation scores by reducing the reward expectation.
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http://dx.doi.org/10.1016/j.bbr.2020.112858DOI Listing
October 2020

Nebivolol for the Treatment of Essential Systemic Arterial Hypertension: A Systematic Review and Meta-Analysis.

Am J Cardiovasc Drugs 2021 Mar;21(2):165-180

Cardiology-Arterial Hypertension Department, Hospital de Clinicas from Universidade Federal do Parana (HC/UFPR), General Carneiro, 181, Curitiba, Paraná, 80060-900, Brazil.

Introduction: Cardiovascular diseases are the main cause of mortality worldwide, and systemic arterial hypertension is associated with a large number of these cases. The objective of health professionals and health policies should be searching for the best therapeutics to control this disease. A recent consensus indicated that β-blockers have recently lost their place in initial indications for the treatment of systemic arterial hypertension and are now more indicated for the treatment of hypertension in association with other clinical situations such as angina, heart failure and arrhythmia; however, it is known that this approach was based on studies that evaluated older β-blockers such as atenolol.

Objective: The main objective of this study was to perform a systematic review with subsequent meta-analysis on the use of nebivolol for hypertensive disease treatment, comparing it with drugs of the main antihypertensive classes.

Methods: This systematic review was based on a search of the MEDLINE (via Pubmed), Scopus, Cochrane, International Pharmaceuticals Abstracts (IPA), and Lilacs databases for randomized and double-blind clinical trials. In addition, we also searched for gray literature studies, to 31 July 2015. Next, a cumulative meta-analysis was performed, with studies being added in a sequential manner, evaluating their impact on the combined effect. For this project, we only meta-analyzed direct comparisons of random effect.

Results: Overall, 981 clinical trials were included in this systematic review. After careful analysis, 34 randomized and double-blind clinical trials were included to investigate the efficacy of nebivolol on systolic (SBP) and diastolic blood pressure (DBP) control and adverse effects. The study population comprised 12,465 patients with systemic arterial hypertension (SAH) aged between 18 and 85 years; 17% of subjects were of Black ethnicity, approximately 55% were men, and almost 10% had diabetes. In SBP management, nebivolol was superior to other β-blockers and diuretics and showed no difference in efficacy when compared with angiotensin receptor blockers or calcium channel blockers. There were insufficient studies on angiotensin-converting enzyme inhibitors for adequate comparison of both SBP and DBP control. For DBP control, nebivolol was more efficient than other β-blockers, angiotensin receptor blockers, diuretics, and calcium channel blockers.

Discussion: Nebivolol is a third-generation β-blocker with additional capabilities to improve blood pressure levels in patients with arterial hypertension, because it acts by additional mechanisms such as endothelium-dependent vasodilation associated with L-arginine and oxide nitric acid, nitric oxide activity on smooth muscle cells, decreasing platelet aggregation, and leukocyte adhesion in the endothelium, decreasing oxidative stress. Although nebivolol has shown good results in controlling hypertension in this study (with few adverse events when compared with placebo treatment) and has an unquestionable benefit in individuals with heart failure (mainly with reduced ejection fraction), there is a lack of studies proving the benefit of this drug for controlling hypertension and reducing clinical outcomes such as cardiovascular (or general) mortality, acute myocardial infarction, or stroke.

Conclusions: Nebivolol demonstrated at least similar control of blood pressure levels in hypertensive individuals when compared with drugs of the most used classes. In addition, in relation to the control of arterial hypertension, studies with clinical outcomes should be performed to ensure the use of this drug in detriment to others with these well-established results.
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http://dx.doi.org/10.1007/s40256-020-00422-0DOI Listing
March 2021

Is shortage of heart donors a real problem? Insights from a Brazilian Mid-West heart transplant program.

J Card Surg 2020 Aug 11;35(8):1802-1810. Epub 2020 Jul 11.

Department of Cardiovascular Surgery, Instituto de Cardiologia do Distrito Federal, Brasilia, Distrito Federal, Brazil.

Background And Aim Of The Study: In developed countries, the shortage of viable donors is the main limiting factor of heart transplantation. The aim of this study is to determine whether the same reality applies to Brazil.

Methods: Between January 2012 and December 2014, 299 adult heart donor offers were studied in terms of donor profiles and reasons for refusal. The European donor scoring system was calculated, being high-risk donors defined as more than 17 points. The donor scoring system was used to objectively determine the donor profile and correlate with donor acceptance and posttransplant primary graft dysfunction and recipient survival. Cox proportional hazard model was used in determining the predictors of long-term mortality.

Results: The rates of donor acceptance and heart transplants performed were 45.8% and 19.3%, respectively. Reasons for refusal were mostly nonmedical (53.7%). The majority of donors were classified as high-risk (65.5%). Hearts from high-risk donors did not impact primary graft dysfunction (14.3% vs 10%; P = .6), neither long-term survival (P = .4 by logrank test). Recipient's age was greater than 50 years (hazard ratio, 6.02; 95% confidence interval, 2.41-16.08; P < .0001) and was the only predictor of long-term mortality.

Conclusions: The shortage of donors is not the main limiting factor of heart transplantation in the Mid-West of Brazil. Nonmedical issues represent the main reason for organ discard. Most of the donors are classified as high risk which indicates that an expanded donor pool is a routine practice in our region, and donor scoring does not seem to influence to proceed with the transplant.
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http://dx.doi.org/10.1111/jocs.14781DOI Listing
August 2020

Penetrated inferior vena cava filter retrieved by open surgery with deep hypothermic circulatory arrest.

J Card Surg 2020 Jul 2;35(7):1642-1643. Epub 2020 Jun 2.

Department of Cardiology, Instituto de Cardiologia do Distrito Federal, Brasilia, Brazil.

Background And Aim: Complications of inferior vena cava filters are relatively common, and they vary according to different filter types and designs. We aim to present a case of penetrated inferior vena cava filter into the liver.

Methods: Case report.

Results: A 42-year old man with thrombophilia (prothrombin gene mutation) required the insertion of an inferior vena cava filter because of recurrent gastrointestinal bleeding associated with oral anticoagulation. However, it penetrated through the retro-hepatic vena cava into the liver, being manifested by constant, blunt abdominal pain. Endovascular retrieval was considered of extreme risk, though a surgical approach was performed under cardiopulmonary bypass with deep hypothermic circulatory arrest. The patient has recovered uneventfully with complete symptom relief.

Conclusions: In symptomatic penetrated vena cava filters in which endovascular retrieval is not feasible, a surgical approach with appropriate planning is a safe and effective treatment.
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http://dx.doi.org/10.1111/jocs.14677DOI Listing
July 2020

Phasic dopamine release identification using convolutional neural network.

Comput Biol Med 2019 11 25;114:103466. Epub 2019 Sep 25.

Department of Informatics, Federal University of Parana, Curitiba, PR, Brazil.

Dopamine has a major behavioral impact related to drug dependence, learning and memory functions, as well as pathologies such as schizophrenia and Parkinson's disease. Phasic release of dopamine can be measured in vivo with fast-scan cyclic voltammetry. However, even for a specialist, manual analysis of experiment results is a repetitive and time consuming task. This work aims to improve the automatic dopamine identification from fast-scan cyclic voltammetry data using convolutional neural networks (CNN). The best performance obtained in the experiments achieved an accuracy of 98.31% using a combined CNN approach. The end-to-end object detection system using YOLOv3 achieved an accuracy of 97.66%. Also, a new public dopamine release dataset was presented, and it is available at https://web.inf.ufpr.br/vri/databases/phasicdopaminerelease/.
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http://dx.doi.org/10.1016/j.compbiomed.2019.103466DOI Listing
November 2019

Anxiety-like behavior induced by 6-OHDA animal model of Parkinson's disease may be related to a dysregulation of neurotransmitter systems in brain areas related to anxiety.

Behav Brain Res 2019 10 26;371:111981. Epub 2019 May 26.

Pharmacology Department, Federal University of Paraná, Brazil. Electronic address:

Anxiety in Parkinson's disease may represent a physiological reaction to the development of other symptoms during disease progression. However, evidence suggests that the incidence of anxiety disorders in Parkinson's disease may be related to neurochemical changes. The present study addresses the question whether dopamine, noradrenaline and serotonin levels in brain structures related to Parkinson's disease and anxiety are responsible for anxiety-like behavior by using an animal model of parkinsonism based in the bilateral injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in the substantia nigra pars compacta. For this, one day after the injection of 6-OHDA, the animals exhibited hypolocomotion and a lower frequency of rearings in the open field test, which was spontaneously reversed on the last day of motor assessment (day 21). The 6-OHDA injection also induced anxiety-like behavior in the elevated plus maze and contextual fear conditioning test (day 21 and 24, respectively). Neurochemical analysis showed a reduction of dopamine and norepinephrine levels in the striatum, prefrontal cortex, and amygdala. In addition, while the serotonin levels were reduced in the striatum and prefrontal cortex, it was increased in the amygdala. The present study indicates that the model of 6-OHDA-induced parkinsonism in rats induced an anxiety-like behavior that may be related to a dysregulation of neurotransmitter systems in brain areas involved with anxiety such as the amygdala, prefrontal cortex and striatum.
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http://dx.doi.org/10.1016/j.bbr.2019.111981DOI Listing
October 2019

Oscillations in cortico-basal ganglia circuits: implications for Parkinson's disease and other neurologic and psychiatric conditions.

J Neurophysiol 2019 07 1;122(1):203-231. Epub 2019 May 1.

Group for Integrative Neurophysiology and Neurotechnology, Department of Experimental Medical Science, Lund University , Lund , Sweden.

Cortico-basal ganglia circuits are thought to play a crucial role in the selection and control of motor behaviors and have also been implicated in the processing of motivational content and in higher cognitive functions. During the last two decades, electrophysiological recordings in basal ganglia circuits have shown that several disease conditions are associated with specific changes in the temporal patterns of neuronal activity. In particular, synchronized oscillations have been a frequent finding suggesting that excessive synchronization of neuronal activity may be a pathophysiological mechanism involved in a wide range of neurologic and psychiatric conditions. We here review the experimental support for this hypothesis primarily in relation to Parkinson's disease but also in relation to dystonia, essential tremor, epilepsy, and psychosis/schizophrenia.
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http://dx.doi.org/10.1152/jn.00590.2018DOI Listing
July 2019

Evaluation of Left-Sided Heart Chambers With Novel Echocardiographic Techniques in Men With Duchenne or Becker Muscular Dystrophy.

Am J Cardiol 2019 03 19;123(6):972-978. Epub 2018 Dec 19.

Cardiology Division, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Parana, Brazil.

Left ventricular systolic dysfunction (LVSD) is a common finding in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies. Novel echocardiographic techniques have been used for the detection of LVSD in several heart diseases. We aim to compare cardiac anatomic and functional data studied by three-dimensional (3DE) and two-dimensional (2DE) echocardiography and to analyze the myocardial strain for the detection of early LVSD in DMD and BMD patients. We performed a cross-sectional study of 46 DMD and 14 BMD patients. We measured left atrium volume and left ventricle volumes and ejection fraction using 3DE and 2DE techniques. Myocardial strain analysis was derived from global longitudinal strain (GLS) measurements. GLS was measured by 2DE with the speckle tracking technique. The correlation between 3DE and 2DE for the measurement of left atrium volume as well as left ventricle diastolic and systolic volumes was strong. 2DE presented larger left atrium and left ventricle volumes. Left ventricle ejection fraction was similar between the two techniques. Myocardial strain analysis was able to detect early LVSD in 50.0% of DMD patients and in 9.1% of BMD patients. In conclusion, two-dimensional echocardiography appears to be a good alternative for the anatomical and functional evaluation of the left heart chambers in DMD and BMD patients. Myocardial strain analysis detects early LVSD in a sizable portion of patients with dystrophinopathies.
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http://dx.doi.org/10.1016/j.amjcard.2018.12.011DOI Listing
March 2019

Is It Conceivable to Still Perform the Cut and Sew Cox Maze III Procedure in the Current Era?

Semin Thorac Cardiovasc Surg 2018 Winter;30(4):429-436. Epub 2018 Aug 8.

Department of Clinical Electrophysiology, Instituto de Cardiologia do Distrito Federal, Brasilia, DF, Brazil.

To determine whether cut and sew Cox maze III procedure is still associated with adequate safety endpoints when performed in conjunction with other open-heart procedures. Between January 2008 and January 2015, 113 consecutive adult patients were submitted to cut and sew Cox maze III procedure in association with other operations for structural heart disease. Mean age was 49 years and 80 (70.8%) were females. Longstanding or persistent atrial fibrillation has occurred in 87.6% and rheumatic heart disease in 80.7%. Valve surgery was performed in 98.2%. The number of associated procedures was correlated with morbidity and hospital mortality. Overall mean cardiopulmonary bypass and aortic cross-clamping times were 129 ± 26 and 105 ± 23 minutes, respectively. Hospital mortality was 1.77%, re-exploration for bleeding 0.9%, cerebrovascular accident 1.8%, and acute renal failure requiring hemodialysis 2.6%. The greater number of associated procedures did not correlate with poorer safety outcomes. Permanent pacemaker was required in 18.2% of those with three associated procedures, as opposed to 4% with two procedures and no requirement with one procedure (P = .01). Frequency of sinus rhythm was 88%, 88%, and 85% at 6, 12, and 24 months, respectively. In a contemporary single-center cohort of predominantly rheumatic patients, the surgical treatment of atrial fibrillation associated with structural heart disease by means of cut and sew Cox maze III procedure is safe, with low morbidity and mortality rates. Surgical complexity, defined by number of associated procedures, did not translate into poorer safety endpoints, except for greater need of permanent pacemaker.
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http://dx.doi.org/10.1053/j.semtcvs.2018.07.006DOI Listing
January 2019

Ethanol Exposure History and Alcoholic Reward Differentially Alter Dopamine Release in the Nucleus Accumbens to a Reward-Predictive Cue.

Alcohol Clin Exp Res 2018 06 30;42(6):1051-1061. Epub 2018 Apr 30.

Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.

Background: Conditioned stimuli (CS) that predict reward delivery acquire the ability to induce phasic dopamine release in the nucleus accumbens (NAc). This dopamine release may facilitate conditioned approach behavior, which often manifests as approach to the site of reward delivery (called "goal-tracking") or to the CS itself (called "sign-tracking"). Previous research has linked sign-tracking in particular to impulsivity and drug self-administration, and addictive drugs may promote the expression of sign-tracking. Ethanol (EtOH) acutely promotes phasic release of dopamine in the accumbens, but it is unknown whether an alcoholic reward alters dopamine release to a CS. We hypothesized that Pavlovian conditioning with an alcoholic reward would increase dopamine release triggered by the CS and subsequent sign-tracking behavior. Moreover, we predicted that chronic intermittent EtOH (CIE) exposure would promote sign-tracking while acute administration of naltrexone (NTX) would reduce it.

Methods: Rats received 14 doses of EtOH (3 to 5 g/kg, intragastric) or water followed by 6 days of Pavlovian conditioning training. Rewards were a chocolate solution with or without 10% (w/v) alcohol. We used fast-scan cyclic voltammetry to measure phasic dopamine release in the NAc core in response to the CS and the rewards. We also determined the effect of NTX (1 mg/kg, subcutaneous) on conditioned approach.

Results: Both CIE and alcoholic reward, individually but not together, associated with greater dopamine to the CS than control conditions. However, this increase in dopamine release was not linked to greater sign-tracking, as both CIE and alcoholic reward shifted conditioned approach from sign-tracking behavior to goal-tracking behavior. However, they both also increased sensitivity to NTX, which reduced goal-tracking behavior.

Conclusions: While a history of EtOH exposure or alcoholic reward enhanced dopamine release to a CS, they did not promote sign-tracking under the current conditions. These findings are consistent with the interpretation that EtOH can stimulate conditioned approach, but indicate that the conditioned response may manifest as goal-tracking.
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http://dx.doi.org/10.1111/acer.13636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984156PMC
June 2018

Diazepam blocks 50 kHz ultrasonic vocalizations and stereotypies but not the increase in locomotor activity induced in rats by amphetamine.

Psychopharmacology (Berl) 2018 07 23;235(7):1887-1896. Epub 2018 Mar 23.

Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, 81.530-980, Brazil.

Rationale: We have recently shown that the benzodiazepine diazepam inhibits dopamine release in the NAc and blocks the increased release of dopamine induced by DL-amphetamine. Rewarding stimuli and many drugs of abuse can induce dopamine release in the nucleus accumbens as well as 50-kHz ultrasonic vocalizations (USVs) in rats.

Objectives: In the present study, we tested the hypothesis that diazepam can also block the increase in locomotor activity and USVs elicited by amphetamine.

Methods: Fifty-kilohertz USVs, stereotypy, and locomotor behavior were scored in adult male Wistar rats treated with i.p. injections of saline, 3 mg/kg DL-amphetamine, 2 mg/kg diazepam, 0.2 mg/kg haloperidol, or a combination of these drugs.

Results: In agreement with previous studies, amphetamine caused significant increases in the number of USV calls, stereotypies, and locomotor activity. The D2 dopamine receptor antagonist haloperidol blocked the effects of amphetamine on USVs, stereotypy, and locomotor activity. Diazepam blocked the effect of amphetamine on USV and stereotypy, but not on horizontal locomotion.

Conclusions: These results suggest that diazepam blocks the rewarding effect of amphetamine. This finding is promising for basic research regarding treatments of substance use disorders and evaluation of the impact of benzodiazepines on motivation.
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http://dx.doi.org/10.1007/s00213-018-4878-8DOI Listing
July 2018

Predictors of early left ventricular systolic dysfunction in duchenne muscular dystrophy patients.

Muscle Nerve 2018 Feb 14. Epub 2018 Feb 14.

Cardiology Division, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Rua General Carneiro, 181-12 º andar Curitiba, 80060-900, Paraná, Brazil.

Introduction: Early detection of left ventricular systolic dysfunction (LVSD) is important for therapeutic strategies for Duchenne muscular dystrophy (DMD) patients. We analyzed myocardial strain using echocardiography for early detection of LVSD and determined the predictors of early LVSD.

Methods: This investigation was a cross-sectional study of 40 DMD patients with normal left ventricular ejection fraction. Global longitudinal strain (GLS) was used to analyze subtle disturbances in longitudinal contraction of the myocardium. Patients were determined to have early LVSD (GLS > -18) or normal left ventricular systolic function (GLS ≤ -18).

Results: Patients who had early LVSD were older and had a higher frequency of corticosteroid therapy and of mutations in exons 45, 46, 47, 48, 49, 50, and 52.

Discussion: Myocardial strain measurements are useful for the early diagnosis of LVSD in DMD patients. Older age, use of corticosteroids, and mutations within the "hot-spot" region of the DMD gene are associated with early LVSD. Muscle Nerve, 2018.
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http://dx.doi.org/10.1002/mus.26102DOI Listing
February 2018

Paracetamol causes endocrine disruption and hepatotoxicity in male fish Rhamdia quelen after subchronic exposure.

Environ Toxicol Pharmacol 2017 Jul 8;53:111-120. Epub 2017 May 8.

Department of Pharmacology, Federal University of Paraná, Box 19031, 81530-990, Curitiba, PR, Brazil. Electronic address:

Paracetamol is one of the most widely sold non-prescription drugs. This study aimed to evaluate the effects of the paracetamol on reproductive, biochemical, genetic, histopathological and hematogical biomarkers by waterborne exposure. Male fish of Rhamdia quelen were exposed to environmental concentrations of paracetamol (0, 0.25, 2.5μg/L) in a semi-static bioassay for 21days. Hemoglobin and hematocrit were reduced upon exposure to 0.25μg/L of paracetamol. Leukocytes and thrombocytes increased after paracetamol exposure. Paracetamol reduced testosterone levels in all exposed groups and increased estradiol levels at higher concentration. Serotonin and dopamine levels increased at exposure to 0.25μg/L. Paracetamol also caused protein carbonyls and increased SOD activity in fish exposed to 2.5μg/L and in addition led to an inhibition of EROD and GST activities in both concentrations. Hepatic genotoxicity occurred at the 0.25μg/L concentration. Hepatic tissues of exposed fish showed mild blood congestion and leucocytes infiltration. The results showed that paracetamol disrupted the hypothalamic-pituitary-gonadal axis, changed hematological parameters and caused hepatotoxicity in Rhamdia quelen. The findings suggest that this drug merits attention relative to its potential endocrine disrupter effect and hepatotoxicity, even at concentrations found in the aquatic environment.
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http://dx.doi.org/10.1016/j.etap.2017.05.005DOI Listing
July 2017

Mechanism for optimization of signal-to-noise ratio of dopamine release based on short-term bidirectional plasticity.

Brain Res 2017 07 8;1667:68-73. Epub 2017 May 8.

Department of Psychology, University of Memphis, Memphis, TN 38152, USA; Neural Engineering Laboratory, Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

Repeated electrical stimulation of dopamine (dopamine) fibers can cause variable effects on further dopamine release; sometimes there are short-term decreases while in other cases short-term increases have been reported. Previous studies have failed to discover what factors determine in which way dopamine neurons will respond to repeated stimulation. The aim of the present study was therefore to investigate what determines the direction and magnitude of this particular form of short-term plasticity. Fixed potential amperometry was used to measure dopamine release in the nucleus accumbens in response to two trains of electrical pulses administered to the ventral tegmental area of anesthetized mice. When the pulse trains were of equal magnitude we found that low magnitude stimulation was associated with short-term suppression and high magnitude stimulation with short-term facilitation of dopamine release. Secondly, we found that the magnitude of the second pulse train was critical for determining the sign of the plasticity (suppression or facilitation), while the magnitude of the first pulse train determined the extent to which the response to the second train was suppressed or facilitated. This form of bidirectional plasticity might provide a mechanism to enhance signal-to-noise ratio of dopamine neurotransmission.
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http://dx.doi.org/10.1016/j.brainres.2017.05.002DOI Listing
July 2017

Partial lesion of dopamine neurons of rat substantia nigra impairs conditioned place aversion but spares conditioned place preference.

Neuroscience 2017 05 7;349:264-277. Epub 2017 Mar 7.

Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81.530-980, PR, Brazil. Electronic address:

Midbrain dopamine neurons play critical roles in reward- and aversion-driven associative learning. However, it is not clear whether they do this by a common mechanism or by separate mechanisms that can be dissociated. In the present study we addressed this question by testing whether a partial lesion of the dopamine neurons of the rat SNc has comparable effects on conditioned place preference (CPP) learning and conditioned place aversion (CPA) learning. Partial lesions of dopamine neurons in the rat substantia nigra pars compacta (SNc) induced by bilateral intranigral infusion of 6-hydroxydopamine (6-OHDA, 3μg/side) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 200μg/side) impaired learning of conditioned place aversion (CPA) without affecting conditioned place preference (CPP) learning. Control experiments demonstrated that these lesions did not impair motor performance and did not alter the hedonic value of the sucrose and quinine. The number of dopamine neurons in the caudal part of the SNc positively correlated with the CPP scores of the 6-OHDA rats and negatively correlated with CPA scores of the SHAM rats. In addition, the CPA scores of the 6-OHDA rats positively correlated with the tissue content of striatal dopamine. Insomuch as reward-driven learning depends on an increase in dopamine release by nigral neurons, these findings show that this mechanism is functional even in rats with a partial lesion of the SNc. On the other hand, if aversion-driven learning depends on a reduction of extracellular dopamine in the striatum, the present study suggests that this mechanism is no longer functional after the partial SNc lesion.
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http://dx.doi.org/10.1016/j.neuroscience.2017.02.052DOI Listing
May 2017

Effects of environmentally relevant concentrations of the anti-inflammatory drug diclofenac in freshwater fish Rhamdia quelen.

Ecotoxicol Environ Saf 2017 May 7;139:291-300. Epub 2017 Feb 7.

Department of Pharmacology, Federal University of Paraná, Box 19031, 81530-980 Curitiba, PR, Brazil. Electronic address:

The presence of pharmaceuticals in the aquatic environment and its impact on humans and the ecosystem are emerging issues in environmental health. This study evaluated the potential biochemical, genetic and reproductive effects of the diclofenac by waterborne exposure, in a semi-static bioassay for 21 days. The fish Rhamdia quelen were exposed to environmental concentrations of diclofenac (0, 0.2, 2 and 20µg/L). The results showed that in the liver, diclofenac reduced the catalase and ethoxyresorufin- O- deethylase activities in fish exposed to 2µg/L, and superoxide dismutase in all exposed groups. The levels of reduced glutathione and glutathione S-transferase (GST) activity increased at all tested concentrations. Lipid peroxidation (LPO) was reduced in the groups exposed to 0.2 and 20µg/L of diclofenac, but there was no protein oxidation. In the testis, the concentration of 0.2µg/L caused major changes as inhibition of SOD, glutathione peroxidase and GST activities and also LPO decrease. Diclofenac was not genotoxic and not altered plasma testosterone and estradiol levels and testicular morphology. In brain, there was a reduction of dopamine and its metabolite DOPAC (3, 4-dihydroxyphenylacetic acid) in exposure to diclofenac, but this not disrupted the hypothalamic-pituitary-gonadal axis.
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http://dx.doi.org/10.1016/j.ecoenv.2017.01.053DOI Listing
May 2017

Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine.

ACS Chem Neurosci 2017 02 26;8(2):300-309. Epub 2017 Jan 26.

Departamento de Farmacologia, Universidade Federal do Paraná , Curitiba 81.530-980, PR, Brazil.

Diazepam is a benzodiazepine receptor agonist with anxiolytic and addictive properties. Although most drugs of abuse increase the level of release of dopamine in the nucleus accumbens, here we show that diazepam not only causes the opposite effect but also prevents amphetamine from enhancing dopamine release. We used 20 min sampling in vivo microdialysis and subsecond fast-scan cyclic voltammetry recordings at carbon-fiber microelectrodes to show that diazepam caused a dose-dependent decrease in the level of tonic and electrically evoked dopamine release in the nucleus accumbens of urethane-anesthetized adult male Swiss mice. In fast-scan cyclic voltammetry assays, dopamine release was evoked by electrical stimulation of the ventral tegmental area. We observed that 2 and 3 mg of diazepam/kg reduced the level of electrically evoked dopamine release, and this effect was reversed by administration of the benzodiazepine receptor antagonist flumazenil in doses of 2.5 and 5 mg/kg, respectively. No significant effects on measures of dopamine re-uptake were observed. Cyclic voltammetry experiments further showed that amphetamine (5 mg/kg, intraperitoneally) caused a significant increase in the level of dopamine release and in the half-life for dopamine re-uptake. Diazepam (2 mg/kg) significantly weakened the effect of amphetamine on dopamine release without affecting dopamine re-uptake. These results suggest that the pharmacological effects of benzodiazepines have a dopaminergic component. In addition, our findings challenge the classic view that all drugs of abuse cause dopamine release in the nucleus accumbens and suggest that benzodiazepines could be useful in the treatment of addiction to other drugs that increase the level of dopamine release, such as cocaine, amphetamines, and nicotine.
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http://dx.doi.org/10.1021/acschemneuro.6b00358DOI Listing
February 2017

Unraveling a new circuitry for sleep regulation in Parkinson's disease.

Neuropharmacology 2016 09 16;108:161-71. Epub 2016 Apr 16.

Laboratório de Neurofisiologia, Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Curitiba, Brazil. Electronic address:

Sleep disturbances are among the most disabling non-motor symptoms in Parkinson's disease. The pedunculopontine tegmental nucleus and basal ganglia are likely involved in these dysfunctions, as they are affected by neurodegeneration in Parkinson's disease and have a role in sleep regulation. To investigate this, we promoted a lesion in the pedunculopontine tegmental nucleus or substantia nigra pars compacta of male rats, followed by 24 h of REM sleep deprivation. Then, we administrated a dopaminergic D2 receptor agonist, antagonist or vehicle directly in the striatum. After a period of 24 h of sleep-wake recording, we observed that the ibotenic acid infusion in the pedunculopontine tegmental nucleus blocked the so-called sleep rebound effect mediated by REM sleep deprivation, which was reversed by striatal D2 receptors activation. Rotenone infusion in the substantia nigra pars compacta also blocked the sleep rebound, however, striatal D2 receptors activation did not reverse it. In addition, rotenone administration decreased the time spent in NREM sleep, which was corroborated by positive correlations between dopamine levels in both substantia nigra pars compacta and striatum and the time spent in NREM sleep. These findings suggest a new circuitry for sleep regulation in Parkinson's disease, involving the triad composed by pedunculopontine nucleus, substantia nigra pars compacta and striatum, evidencing a potential therapeutic target for the sleep disturbances associated to this pathology.
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http://dx.doi.org/10.1016/j.neuropharm.2016.04.018DOI Listing
September 2016

Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

Behav Brain Res 2016 Mar 18;301:43-54. Epub 2015 Dec 18.

Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil; Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address:

Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity.
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http://dx.doi.org/10.1016/j.bbr.2015.12.011DOI Listing
March 2016

Exercise Improves Cognitive Impairment and Dopamine Metabolism in MPTP-Treated Mice.

Neurotox Res 2016 Jan;29(1):118-25

The classical motor symptoms of Parkinson’s disease (PD) are preceded by non-motor symptoms in preclinical stages, including cognition impairment. The current drug treatment for PD is palliative and does not meet the clinical challenges of the disease, such as levodopa-induced dyskinesia, non-motor symptoms, and neuroprotection. We investigated the neuroprotective and disease-modifying potential of physical exercise in a preclinical animal model of PD. C57BL/6 mice (adult males) ran on a horizontal treadmill for 6 weeks (moderate intensity, 5 times/week) and were treated intranasally with 65 mg/kg of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Exercise did not protect against MPTP-induced nigrostriatal neurodegeneration or frontostriatal dopamine depletion but decreased striatal dopamine turnover. Exercise also attenuated procedural and working memory impairment and D2 receptor hypersensitivity in MPTP-treated mice. In summary, exercise improved dopaminergic neurotransmission and enhanced cognition in a preclinical animal model of PD.
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http://dx.doi.org/10.1007/s12640-015-9566-4DOI Listing
January 2016

Role of brainstem serotonin in analgesia produced by low-intensity exercise on neuropathic pain after sciatic nerve injury in mice.

Pain 2015 Dec;156(12):2595-2606

Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Trindade, Florianopolis, Brazil Graduate Program in Neuroscience, Center of Biological Sciences, Federal University of Santa Catarina, Trindade, Florianopolis, Brazil Laboratory of Molecular and Behavioral Neurobiology, Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Trindade, Florianopolis, Brazil Department of Physical Therapy and Rehabilitation Science, Pain Research Program, University of Iowa, Iowa City, IA, USA.

Physical exercise is a low-cost, safe, and efficient intervention for the reduction of neuropathic chronic pain in humans. However, the underlying mechanisms for how exercise reduces neuropathic pain are not yet well understood. Central monoaminergic systems play a critical role in endogenous analgesia leading us to hypothesize that the analgesic effect of low-intensity exercise occurs through activation of monoaminergic neurotransmission in descending inhibitory systems. To test this hypothesis, we induced peripheral nerve injury (PNI) by crushing the sciatic nerve. The exercise intervention consisted of low-intensity treadmill running for 2 weeks immediately after injury. Animals with PNI showed an increase in pain-like behaviors that were reduced by treadmill running. Reduction of serotonin (5-hydroxytryptamine) synthesis using the tryptophan hydroxylase inhibitor para-chlorophenylalanine methyl ester prevented the analgesic effect of exercise. However, blockade catecholamine synthesis with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine had no effect. In parallel, 2 weeks of exercise increased brainstem levels of the 5-HT and its metabolites (5-hydroxyindoleacetic acid), decreased expression of the serotonin transporter, and increased expression of 5-HT receptors (5HT-1B, 2A, 2C). Finally, PNI-induced increase in inflammatory cytokines, tumor necrosis factor-alpha, and interleukin-1 beta, in the brainstem, was reversed by 2 weeks of exercise. These findings provide new evidence indicating that low-intensity aerobic treadmill exercise suppresses pain-like behaviors in animals with neuropathic pain by enhancing brainstem 5-HT neurotransmission. These data provide a rationale for the analgesia produced by exercise to provide an alternative approach to the treatment of chronic neuropathic pain.
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http://dx.doi.org/10.1097/j.pain.0000000000000372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666012PMC
December 2015

The importance of lactic acid in migraines and fibromyalgia.

Rev Bras Reumatol 2015 Nov-Dec;55(6):471-6. Epub 2015 Aug 1.

Programa de Pós-Graduação de Medicina Interna e Ciências da Saúde, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brasil; Neuromuscular/Neurologia, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brasil. Electronic address:

Background: Lactic acid is a byproduct of both muscle metabolism and the central nervous system. Changes in metabolism are related to various physiological and pathological conditions. The aim of this study was to determine the relationship between migraine and fibromyalgia with the levels of lactic acid in the blood.

Methods: We study of 93 patients was divided into five groups: 1) patients with fibromyalgia (n=20); 2) episodic migraine (n=20); 3) chronic migraine (n=20); 4) fibromyalgia and episodic migraine (n= 13); and 5) fibromyalgia and chronic migraine (n=20), and 20 healthy subjects (control group). Blood levels of lactic acid were measured at four different time points: at rest, during aerobic exercise, during anaerobic physical activity and while resting after anaerobic exercise.

Results: Lactic acid increased in all groups during anaerobic physical activity without predominance for either group. During aerobic physical activity, all groups increased lactic acid levels, but the increase was more expressive in the chronic migraine group and the chronic migraine with fibromyalgia group without statistical significance.

Conclusions: We did not found abnormalities involving the metabolism of lactic acid in episodic and chronic migraine with or without fibromyalgia.
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http://dx.doi.org/10.1016/j.rbr.2015.02.002DOI Listing
May 2018

Unusual mechanism of myocardial infarction in prosthetic valve endocarditis.

Int Med Case Rep J 2015 25;8:111-6. Epub 2015 May 25.

Department of Cardiovascular Medicine, Instituto de Cardiologia do Distrito Federal, Fundação Universitária de Cardiologia, Brasília, Distrito Federal, Brazil.

A 46-year-old man with bicuspid aortic valve and severe calcific aortic stenosis was submitted to aortic valve replacement with a stented bioprosthesis. He developed Staphylococcus epidermidis prosthetic valve endocarditis a month later, presenting in the emergency room with acute myocardial infarction. The mechanism of myocardial ischemia was a large aortic root abscess causing left main extrinsic compression. He was urgently taken to the operating room, and an aortic root replacement with cryopreserved homograft was performed, associated with autologous pericardium patch closure of aortic to right atrium fistula and coronary artery bypass grafting of the left anterior descending. After a difficult postoperative period with multiple problems, he was eventually discharged home. At 36-month follow-up, he is asymptomatic with no recurrent infection, and the left main coronary artery is widely patent on control chest computed tomography.
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http://dx.doi.org/10.2147/IMCRJ.S61348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448920PMC
June 2015

Outcome of patients with high-risk Duke treadmill score and normal myocardial perfusion imaging on spect.

J Nucl Cardiol 2016 12 3;23(6):1291-1300. Epub 2015 Jun 3.

Quanta - Diagnóstico e Terapia, R. Almirante Tamandaré, 1000, Curitiba, PR, CEP 80045-170, Brazil.

Background: Annual mortality rate can range from <1% for patients with normal myocardial perfusion by SPECT to >5% based on a high-risk Duke treadmill score (DTS). Information on the prognosis of patients with the combination of HRDTS and normal SPECT is limited and is the purpose of this study.

Methods: Data from a large nuclear cardiology registry (n = 17,972 patients) were reviewed. A total of 340 had HRDTS (score ≤ -11) while undergoing SPECT. Combined cardiovascular mortality and non-fatal myocardial infarction (MI) and cardiovascular mortality alone were available in 310 patients at a mean follow-up of 4.01 ± 1.5 years.

Results: The majority of the patients had abnormal SPECT (n = 270, 71%). The abnormal SPECT patients compared to the normal were older (65.6 vs 62.8 years of age; P = .025), more likely to have abnormal left ventricular ejection fraction (26.1% vs 0%; P < .0001), known coronary artery disease (CAD, 35.9% vs 7.8%; P < .0001) and lower DTS (-14.5 vs -13.2; P = .0006), Kaplan-Meier survival analysis demonstrated a significantly lower cardiovascular mortality (5.4% vs 0%, P = .02) and combined outcome of MI and cardiovascular mortality (15% vs 4.4%, P = .009) in patients with normal versus abnormal SPECT.

Conclusions: High-risk DTS is associated with abnormal perfusion SPECT in most patients, but nearly one-third of the patients had normal perfusion. Patients with a normal SPECT had a lower cardiovascular event rates.
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http://dx.doi.org/10.1007/s12350-015-0156-xDOI Listing
December 2016

The mechanism of antidepressant-like effects of piroxicam in rats.

J Pharmacol Pharmacother 2015 Jan-Mar;6(1):7-12

Department of Pharmacology, Federal University of Paraná, Brazil.

Objective: To investigate the antidepressant-like effect of piroxicam with a focus on serotonergic neurotransmission.

Materials And Methods: Rats were randomly distributed into the following groups: 0.9% saline control; 3 mg/kg pizotifen; 10 mg/kg sertraline; 10 mg/kg piroxicam; 10 mg/kg sertraline + 10 mg/kg piroxicam; 10 mg/kg sertraline + 3 mg/kg pizotifen; and 10 mg/kg piroxicam + 3 mg/kg pizotifen. All the drugs were dissolved in 0.9% saline. Three administrations of the drugs (piroxicam and sertraline) were performed 1, 5 and 24 h before testing the animals in the open field followed by the forced swim test (FST). Piroxicam and sertraline were administered orally by gavage and pizotifen was administered intraperitoneally 30 min before gavage. Immediately after the FST, the hippocampi were rapidly dissected for neurochemical analysis in high-performance liquid chromatography.

Results: Acute treatment with piroxicam promoted an antidepressant-like effect in the FST, which was associated with an increase in serotonin levels in the hippocampus. This effect was potentiated in the piroxicam + sertraline group but counteracted by administration of the non-selective serotonin receptor antagonist pizotifen.

Conclusion: These results suggest that the antidepressant-like effect of piroxicam in the FST is mediated by the serotonin system; however, by different mechanisms from those of sertraline.
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http://dx.doi.org/10.4103/0976-500X.149133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319255PMC
February 2015

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation.

Neurosci Biobehav Rev 2015 Nov 12;58:186-210. Epub 2015 Feb 12.

Department of Psychology, The University of Memphis, Memphis, TN, USA. Electronic address:

This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms.
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http://dx.doi.org/10.1016/j.neubiorev.2015.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534367PMC
November 2015

Activation of postsynaptic D2 dopamine receptors in the rat dorsolateral striatum prevents the amnestic effect of systemically administered neuroleptics.

Behav Brain Res 2015 Mar 26;281:283-9. Epub 2014 Dec 26.

Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81531-980, PR, Brazil. Electronic address:

Systemically administered antipsychotics bind to dopamine (DA) D2 receptors expressed in both pre- and postsynaptic neurons of different striatal sites and present an amnestic effect on learning and memory of conditioned avoidance responses (CAR). The aim of this study was to test whether blockade of the pre- or post-synaptic D2 receptors of the dorsolateral striatum of rats is the mechanism by which systemically administered antipsychotics present this amnestic effect. CAR learning and memory was evaluated in rats that received i.p. administrations of pre- or postsynaptic doses of the antipsychotic sulpiride combined with intra-DLS infusion of the D2 agonist quinpirole. Intra-DLS quinpirole itself was not amnestic and this effect was prevented by co-administration of presynaptic dose of sulpiride. However, sulpiride was amnestic when administered systemically in a post- but not presynaptic dose. This amnestic effect of sulpiride was prevented by the co-administration of quinpirole into the DLS. These results show that a blockade of postsynaptic D2 receptors in the DLS is necessary and sufficient to produce the amnestic effect of neuroleptics on CARs.
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http://dx.doi.org/10.1016/j.bbr.2014.12.040DOI Listing
March 2015