Publications by authors named "Angelica Rocha"

19 Publications

  • Page 1 of 1

Primary conjunctival sporotrichosis in three cats from Northeastern Brazil.

Vet Ophthalmol 2021 Mar 19;24(2):209-215. Epub 2021 Feb 19.

Departamento de Morfologia e Fisiologia Animal, Universidade Federal Rural de Pernambuco, Brasil.

Introduction: Classically, sporotrichosis occurs as a chronic granulomatous lymphocutaneous infection. The extracutaneous form is uncommon and may affect the eye without cutaneous involvement. The most frequent form of ocular sporotrichosis reported in humans is a granulomatous conjunctivitis. There are no previous reports on primary ocular sporotrichosis in cats.

Procedures: Three mixed breed cats rescued from shelters were referred by the veterinarian for ophthalmic evaluation with a complaint of conjunctivitis nonresponsive to treatment with no evidence of skin disease or systemic disease. Complete ophthalmic examination, conjunctival cytology, and microbiological analysis were performed.

Results: Ophthalmic examinations revealed epiphora, purulent ocular discharge, conjunctival hyperemia, and a mass in the palpebral conjunctiva. Conjunctival cytology revealed segmented and degenerated neutrophils, conjunctival epithelial cells, and an abundant number of round and oval cells compatible with Sporothrix spp. Microbiological culture was performed and confirmed the presence of fungi from the Sporothrix schenckii complex. All animals were treated with oral itraconazole; two animals received topical itraconazole in association with oral treatment. Case 1 was refractory to treatment, and iodate potassium was combined with itraconazole therapy without resolution at the time of this publication. Cases 2 and 3 had complete resolution of conjunctival lesions with four months of oral and topical itraconazole therapy.

Conclusion: Conjunctival sporotrichosis should be considered as a differential diagnosis of conjunctivitis in cats from endemic regions. Conjunctival cytology is an important tool that can aid early diagnosis.
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http://dx.doi.org/10.1111/vop.12865DOI Listing
March 2021

Polymorphisms of the genes CTLA4, PTPN22, CD40, and PPARG and their roles in Graves' disease: susceptibility and clinical features.

Endocrine 2021 Jan 17;71(1):104-112. Epub 2020 May 17.

Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Purpose: CTLA4, PTPN22, and CD40 are immune-regulatory genes strongly associated with GD, as well as PPARG, but their clinical significance in different populations is still uncertain.

Methods: We genotyped 282 Brazilian GD patients (234 women and 48 men, 39.80 ± 11.69 years old), including 144 patients with GO, and 308 healthy control individuals (246 women and 62 men, 36.86 ± 12.95 years old).

Results: A multivariate analysis demonstrated that the inheritance of the GG genotype rs3087243 of CTLA4 (OR = 2.593; 95% CI = 1.630-4.123; p < 0.0001) and the CC genotype of rs3789607 of PTPN22 (OR = 2.668; 95% CI = 1.399-5.086; p = 0.0029) consisted in factors independent of the susceptibility to GD. The inheritance of polymorphic genotypes of rs5742909 of CTLA4 was associated with older age at the time of diagnosis (42.90 ± 10.83 versus 38.84 ± 11.81 years old; p = 0.0105), with higher TRAb levels (148.17 ± 188.90 U/L versus 112.14 ± 208.54 U/L; p = 0.0229) and the need for higher therapeutic doses of radioiodine (64.23 ± 17.16 versus 50.22 ± 16.86; p = 0.0237). The inheritance of the CC genotype of rs1883832 CD40 gene was more frequent among women (69.65%) than men (52.00%; p = 0.0186). The polymorphic genotype of PPARG gene (rs1801282) was associated with TPOAb positivity (p = 0.0391), and the GG genotype of rs2476601 of PTPN22 gene was associated with positivity for both TgAb (p = 0.0360) and TPOAb (p < 0.0001). Both polymorphic genotypes rs2476601 and rs3789607 of the PTPN22 gene were more frequent among nonsmoking patients (p = 0.0102 and p = 0.0124, respectively).

Conclusions: Our data confirm the important role of CTLA4 polymorphisms in GD susceptibility; demonstrate the role of PTPN22 polymorphisms in patients' clinical features; and suggest these genes may influence the severity of the disease.
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http://dx.doi.org/10.1007/s12020-020-02337-xDOI Listing
January 2021

Mechanism of iron ions sorption by chitosan-genipin films in acidic media.

Carbohydr Polym 2020 May 20;236:116026. Epub 2020 Feb 20.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; CICECO, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address:

Chitosan-genipin (Ch-Ge) films have been proposed as wine preservative due to their capacity to uptake iron ions. The wine is an aqueous acidic solution of water and ethanol, whose acidity derives from tartaric acid. This acid has been shown to form negatively charged iron-tartrate complexes able to interact with the positively charged amine groups of chitosan, removing the iron ions from solutions. Nevertheless, it is possible that these films can uptake iron ions in the presence of other carboxylic acids. To understand the iron-binding capacity of Ch-Ge films, aqueous solutions of different carboxylic acids were prepared in the presence of iron ions and Ch-Ge films. It was observed that the Ch-Ge films only presented sorption capacity at pH 3.5 in the presence of α-hydroxypolycarboxylic acids, through electrostatic interactions. These results allow proposing a broad application of Ch-Ge films to beverages and other liquids containing malic, tartaric or citric acids.
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http://dx.doi.org/10.1016/j.carbpol.2020.116026DOI Listing
May 2020

Neurotoxicity of low-level lead exposure: History, mechanisms of action, and behavioral effects in humans and preclinical models.

Neurotoxicology 2019 07 2;73:58-80. Epub 2019 Mar 2.

California State University San Marcos, San Marcos, CA 92069, USA.

Lead is a neurotoxin that produces long-term, perhaps irreversible, effects on health and well-being. This article summarizes clinical and preclinical studies that have employed a variety of research techniques to examine the neurotoxic effects of low levels of lead exposure. A historical perspective is presented, followed by an overview of studies that examined behavioral and cognitive outcomes. In addition, a short summary of potential mechanisms of action is provided with a focus on calcium-dependent processes. The current level of concern, or reference level, set by the CDC is 5 μg/dL of lead in blood and a revision to 3.5 μg/dL has been suggested. However, levels of lead below 3 μg/dL have been shown to produce diminished cognitive function and maladaptive behavior in humans and animal models. Because much of the research has focused on higher concentrations of lead, work on low concentrations is needed to better understand the neurobehavioral effects and mechanisms of action of this neurotoxic metal.
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http://dx.doi.org/10.1016/j.neuro.2019.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462347PMC
July 2019

Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration.

Pharmacol Biochem Behav 2017 06 22;157:24-34. Epub 2017 Apr 22.

Office for Training Research, and Education in the Sciences, California State University San Marcos, CA 92096, USA; Department of Psychology, California State University San Marcos, CA 92096, USA. Electronic address:

Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known of the effects of drugs in adolescence, and differences in response between adolescents and adults. PCP and ketamine are popular club drugs, both possessing rewarding properties that could lead to escalating use. Drug sensitization (or reverse tolerance), which refers to an increase in an effect of a drug following repeated use, has been linked with the development of drug cravings that is a hallmark of addiction. The current work investigated the acute response and the development of sensitization to PCP and ketamine in adolescent and adult rats. Periadolescent Sprague-Dawley rats (30days or 38days of age), and young adults (60days of age) received PCP (6mg/kg IP) or ketamine (20mg/kg IP) once every three days, for a total of five drug injections. Adolescents and adults showed a stimulant response to the first injection of either drug, however the response was considerably greater in the youngest adolescents and lowest in the adults. With repeated administration, adults showed a robust escalation in activity that was indicative of the development of sensitization. Adolescents showed a flatter trajectory, with similar high levels of activity following an acute treatment and after five drug treatments. The results demonstrate important distinctions between adolescents and adults in the acute and repeated effects of PCP and ketamine.
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http://dx.doi.org/10.1016/j.pbb.2017.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540233PMC
June 2017

Revisiting the structural features of arabinoxylans from brewers' spent grain.

Carbohydr Polym 2016 Mar 11;139:167-76. Epub 2015 Dec 11.

QOPNA, Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal.

The brewers' spent grain (BSG) arabinoxylans (AX) have been described to be composed by a backbone of (β1→4)-linked xylose residues containing only single units of arabinose as side chains. However, this is not in accordance with the structural features of AX from other cereal sources. Aiming to disclose the possibility of additional structural details, fractions enriched in AX were obtained by sequential extraction from BSG. The AX richest fraction was hydrolysed with xylanase, fractioned by size-exclusion chromatography, and analysed by electrospray tandem mass spectrometry (ESI-MS(n)). Methylation analysis showed that the amount of terminally linked arabinose residues was not in accordance with the number of xylose branching points. This was due to the presence of O-acetyl, hexose, hexuronic acid, and methylated uronic acid residues. AXs presenting these structural features can be a potential source of a large screening prebiotic, providing, in the same molecule, areas of fast and slow probiotic fermentation rates.
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http://dx.doi.org/10.1016/j.carbpol.2015.12.006DOI Listing
March 2016

High pressure treatments accelerate changes in volatile composition of sulphur dioxide-free wine during bottle storage.

Food Chem 2015 Dec 2;188:406-14. Epub 2015 May 2.

QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

The impact of high hydrostatic pressure (HHP) treatments on volatile composition of sulphur dioxide-free wines during bottle storage was studied. For this purpose, white and red wines were produced without sulphur dioxide (SO2) and, at the end of the alcoholic fermentation, the wines were pressurised at 500 MPa and 425 MPa for 5 min. Wine with 40 ppm of SO2 and a wine without a preservation treatment were used as controls. More than 160 volatile compounds, distributed over 12 chemical groups, were identified in the wines by an advanced gas chromatography technique. The pressurised wines contained a higher content of furans, aldehydes, ketones, and acetals, compared with unpressurised wines after 9 months of storage. The changes in the volatile composition indicate that HHP treatments accelerated the Maillard reaction, and alcohol and fatty acid oxidation, leading to wines with a volatile composition similar to those of faster aged and/or thermally treated wines.
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http://dx.doi.org/10.1016/j.foodchem.2015.05.002DOI Listing
December 2015

Microwave superheated water and dilute alkali extraction of brewers' spent grain arabinoxylans and arabinoxylo-oligosaccharides.

Carbohydr Polym 2014 Jan 6;99:415-22. Epub 2013 Sep 6.

QOPNA, Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal. Electronic address:

Microwave superheated water extractions (MWE) were performed to evaluate the feasibility of this technology for quantitative recovery of the arabinoxylans (AX) or arabinoxylo-oligosaccharides (AXOS) from brewers' spent grain (BSG). The AX+AXOS yield increased with the increase of the temperature in the range from 140 to 210 °C during 2 min. The higher temperatures promoted depolymerisation, debranching, and deesterification of the polysaccharides, with formation of brown products. The conditions that promote a compromise between the yield and the structure obtained, minimizing the thermal degradation of the fractions extracted by MWE are the following: (1) 140 °C, to remove the residual starch mixed with β-glucans; (2) Suspension of the residue left in water and treated at 180 °C; (3) suspension of the residue in 0.1 M KOH and treated at 180 °C. Using this sequential procedure, it was possible to extract 62% of BSG AX+AXOS, presenting degrees of polymerization ranging between 7 and 24 xylose residues, and a degree of phenolic acids esterification between 5 and 21%. The structural variability obtained by MWE allows defining specific types of compounds for different applications and uses depending on the extraction conditions used.
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http://dx.doi.org/10.1016/j.carbpol.2013.09.003DOI Listing
January 2014

Case for diagnosis.

An Bras Dermatol 2012 May-Jun;87(3):491-2

Medical School, Federal University of Minas Gerais, Belo Horizonte, Brazil.

An 80-year-old Caucasian male patient was referred for evaluation of a rapidly growing, asymptomatic, erythematous nodule measuring 2 cm in diameter on his left cheek. The lesion had been present for four months. Dermoscopy revealed a homogeneous pink background with polymorphous telangiectatic vessels. Histopathology showed tumors in the deep dermis and subcutis composed of round cells with scant cytoplasm. Immunohistochemical staining was positive for CK20 confirming the diagnosis of Merkel cell carcinoma.
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http://dx.doi.org/10.1590/s0365-05962012000300027DOI Listing
March 2013

Role of the prefrontal cortex and nucleus accumbens in reinstating methamphetamine seeking.

Eur J Neurosci 2010 Mar 17;31(5):903-9. Epub 2010 Feb 17.

Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, BSB410SC, Charleston, SC 29425, USA.

Although the involvement of the medial prefrontal cortex projection to the nucleus accumbens in the reinstatement of cocaine seeking has been well studied, it is not known if this projection plays a similar role in the reinstatement of cue- and methamphetamine-induced drug seeking in animals extinguished from methamphetamine self-administration. Accordingly, following extinction from long-access methamphetamine self-administration, rats were bilaterally microinjected with either a combination of the GABA agonists baclofen/muscimol or vehicle (artificial cerebrospinal fluid) into the infralimbic or prelimbic subcompartments of the medial prefrontal cortex or into the shell or core subcompartments of the nucleus accumbens. Similar to cocaine seeking, inactivation of either the prelimbic cortex or accumbens core eliminated cue- and methamphetamine-induced reinstatement, and inactivation of neither the infralimbic cortex nor shell subcompartments inhibited methamphetamine-induced drug seeking. However, in contrast to previous reports with cocaine, cue-induced reinstatement of methamphetamine seeking was inhibited by inactivation of the infralimbic cortex. In conclusion, although a primary role in reinstated drug seeking by the prelimbic and the accumbens core is similar between cocaine and methamphetamine, the recruitment of the infralimbic cortex by conditioned cues differs between these two psychostimulant drugs.
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http://dx.doi.org/10.1111/j.1460-9568.2010.07134.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346145PMC
March 2010

Extended methamphetamine self-administration in rats results in a selective reduction of dopamine transporter levels in the prefrontal cortex and dorsal striatum not accompanied by marked monoaminergic depletion.

J Pharmacol Exp Ther 2009 Nov 31;331(2):555-62. Epub 2009 Jul 31.

Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

Chronic abuse of methamphetamine leads to cognitive dysfunction and high rates of relapse, paralleled by significant changes of brain dopamine and serotonin neurotransmission. Previously, we found that rats with extended access to methamphetamine self-administration displayed enhanced methamphetamine-primed reinstatement of drug-seeking and cognitive deficits relative to limited access animals. The present study investigated whether extended access to methamphetamine self-administration produced abnormalities in dopamine and serotonin systems in rat forebrain. Rats self-administered methamphetamine (0.02-mg/i.v. infusion) during daily 1-h sessions for 7 to 10 days, followed by either short- (1-h) or long-access (6-h) self-administration for 12 to 14 days. Lever responding was extinguished for 2 weeks before either reinstatement testing or rapid decapitation and tissue dissection. Tissue levels of monoamine transporters and markers of methamphetamine-induced toxicity were analyzed in several forebrain areas. Long-access methamphetamine self-administration resulted in escalation of daily drug intake ( approximately 7 mg/kg/day) and enhanced drug-primed reinstatement compared with the short-access group. Furthermore, long-, but not short-access to self-administered methamphetamine resulted in persistent decreases in dopamine transporter (DAT) protein levels in the prefrontal cortex and dorsal striatum. In contrast, only minor alterations in the tissue levels of dopamine or its metabolites were found, and no changes in markers specific for dopamine terminals or glial cell activation were detected. Our findings suggest that persistent methamphetamine seeking is associated with region-selective changes in DAT levels without accompanying monoaminergic neurotoxicity. Greater understanding of the neuroadaptations underlying persistent methamphetamine seeking and cognitive deficits could yield targets suitable for future therapeutic interventions.
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http://dx.doi.org/10.1124/jpet.109.155770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775260PMC
November 2009

Developmental lead exposure attenuates methamphetamine dose-effect self-administration performance and progressive ratio responding in the male rat.

Pharmacol Biochem Behav 2008 Jun 8;89(4):508-14. Epub 2008 Feb 8.

Department of Psychology, Texas A&M University, College Station, TX 77843, United States.

Perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse [Nation J.R., Cardon A.L., Heard H.M., Valles R., Bratton G.R. Perinatal lead exposure and relapse to drug-seeking behavior in the rat: a cocaine reinstatement study. Psychopharmacol 2003;168: 236-243.; Nation J.R., Smith K.R., Bratton G.R. Early developmental lead exposure increases sensitivity to cocaine in a self-administration paradigm. Pharmacol Biochem Behave 2004; 77: 127-13; Rocha A., Valles R., Cardon A.L., Bratton G.R., Nation J.R. Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead. Neuropsychopharmacol 2005; 30: 2058-2064.]. However, changes in sensitivity to methamphetamine across the phases of drug abuse have not been examined in animals perinatally exposed to lead. Because the mainstream popularity of methamphetamine in the United States is increasing and lead exposure continues to be widespread, an examination of this drug and how it may be modified by perinatal exposure to lead is warranted. The studies reported here examined the effects of perinatal lead exposure on adult self-administration of intravenous (i.v.) methamphetamine across the maintenance phase of drug addiction. Experiment 1 examined dose-effect patterns in control and lead-exposed animals. Experiment 2 evaluated control and lead-exposed animals in a progressive ratio task. Female rats were administered a 16-mg lead or a control solution for 30 days prior to breeding with non-exposed males. Exposure continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults (PND 70) and subsequently were randomly assigned to one of the two studies, using only one male rat per litter for each study. The data showed a general attenuation of the reinforcement efficacy of methamphetamine in animals perinatally exposed to lead, as compared to control animals.
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http://dx.doi.org/10.1016/j.pbb.2008.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895984PMC
June 2008

Developmental lead exposure alters methamphetamine self-administration in the male rat: acquisition and reinstatement.

Drug Alcohol Depend 2008 May 1;95(1-2):23-9. Epub 2008 Feb 1.

Department of Psychology, Texas A&M University, College Station, TX 77843, USA.

The rate of acquisition of drug self-administration and the return to drug seeking are important elements of the overall drug profile, and are essential factors in understanding risks associated with drug abuse. Experiment 1 examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous (i.v.) methamphetamine self-administration. Experiment 2 investigated the effects of perinatal lead exposure on drug-maintained responding in a reinstatement (relapse) paradigm. In Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Lead exposure continued through gestation and lactation and was discontinued at weaning (postnatal day [PND] 21). Male rats born to control or lead-exposed dams were tested daily as adults in an acquisition paradigm that incorporated both Pavlovian and operant components. An initial 3-h autoshaping period preceded a 3-h self-administration period. For 35 daily training sessions i.v. methamphetamine infusions [inf] (0.02 mg/kg) were paired with the extension and retraction of a lever (autoshaping), while inf occurred during self-administration only when a lever press was executed (FR-1). In Experiment 2 animals developmentally exposed to lead were trained on an FR-2 to self-administer methamphetamine (0.04 mg/kg/inf) and then placed on an extinction schedule prior to receiving intraperitoneal (i.p.) priming injections of saline, 0.50, 1.00, or 1.50 mg/kg methamphetamine. The findings from Experiment 1 showed that acquisition was delayed in rats born to lead-exposed dams gavaged daily with 16 mg lead throughout gestation and lactation when a 0.02-mg/kg/inf of methamphetamine served as the reinforcement outcome. Additional data from Experiment 2 indicated priming cues (injections of methamphetamine [i.p.]) administered after extinction were less likely to occasion a return to drug seeking (relapse) in the 16-mg group relative to the 0-mg control group. These results suggest perinatal lead exposure alters patterns of methamphetamine self-administration during the adult cycle.
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http://dx.doi.org/10.1016/j.drugalcdep.2007.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891033PMC
May 2008

The effects of concurrent administration of +/-3,4-methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat.

Pharmacol Biochem Behav 2007 Dec 8;88(2):165-70. Epub 2007 Aug 8.

Department of Psychology, Texas A&M University, College Station, TX 77843, United States.

Conditioned place preference (CPP), a commonly used model for studying the role of contextual cues in drug reward and drug seeking, was employed to explore possible behavioral interactions between (+/-)3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") and cocaine. On each of four occasions, adult male rats received one of three doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg; administered subcutaneously [s.c.]) combined with one of three doses of cocaine (0 mg/kg, 2.5 mg/kg, 5 mg/kg; administered intraperitoneally [i.p.]), and were then tested in a CPP paradigm. The results showed MDMA-induced CPP at a unit dose of 5 mg/kg, but at the 10 mg/kg dose there was a return to baseline (control) performance levels. For cocaine alone, CPP increased in a linear fashion as the drug dose was increased. Concurrent administration resulted in antagonism of each drug, but there was evidence that this pattern was reversible at higher doses of the respective drugs. These data are instructive insofar as they suggest that the behavioral and neurochemical effects of MDMA and cocaine presented in isolation are dramatically altered when the two drugs are presented in combination.
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http://dx.doi.org/10.1016/j.pbb.2007.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878136PMC
December 2007

The effects of acquisition training schedule on extinction and reinstatement of cocaine self-administration in male rats.

Exp Clin Psychopharmacol 2006 May;14(2):245-53

Department of Psychology, Texas A&M University, College Station, 77843, USA.

Partial reinforcement is known to increase resistance to extinction (Rn) relative to training with continuous reinforcement. This phenomenon, referred to as the partial reinforcement extinction effect, is one of the most robust in learning and conditioning studies. Experiment 1 investigated manipulations known to affect the partial reinforcement extinction effect and determined their possible relevance for drug use patterns. Male rats received intravenous cocaine self-administration training under partial reinforcement (FR-10) training or continuous reinforcement (FR-1) conditions with either a low (0.25 mg/kg infusion) or a high cocaine dose (1.00 mg/kg infusion). Animals were placed on an extinction (recurrent nonreward) schedule for 10 days (1-hr sessions) prior to being tested for cue-induced reinstatement (single 2-hr session). Experiment 2 involved acquisition of cocaine self-administration under FR-1 conditions of short training (15 days) or extended training (30 days) with a low dose (0.25 mg/kg infusion) or a medium dose (0.50 mg/kg infusion) of cocaine reward prior to extinction or reinstatement. Experiment 1 showed that rats trained with FR-10-high dose outcomes exhibited greater Rn than the remaining groups. Additionally, FR-10-high dose and FR-10-low dose rats were more likely to return to active drug seeking during the reinstatement test. In Experiment 2, rats trained under FR-1-medium dose conditions were more persistent during extinction following short acquisition training than comparable rats experiencing extended acquisition training. The reinstatement test was conducted following extinction, in which it was observed that overtraining under FR-1-medium dose reward schedules resulted in a decrease in the tendency to return to active drug seeking.
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http://dx.doi.org/10.1037/1064-1297.14.2.245DOI Listing
May 2006

Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead.

Neuropsychopharmacology 2005 Nov;30(11):2058-64

Department of Psychology, Texas A&M University, College Station, TX 77843, USA.

The rate of acquisition of drug self-administration may serve as a predictor of later drug-taking behavior, possibly influencing the vulnerability to use drugs. The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous cocaine self-administration using an automated procedure that included both Pavlovian and operant components. For Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning (postnatal day (PND) 21). Animals born to control or lead-exposed dams subsequently were tested daily as adults in a preparation where sessions included an initial 3-h autoshaping period followed by a 3-h self-administration period where 0.20 mg/kg cocaine was delivered contingently. During autoshaping, intravenous cocaine infusions were paired with the extension and retraction of a lever, while infusions occurred during self-administration only when a lever press was executed (FR-1). The criterion for acquisition was a 2-day period during which a mean of 50 infusions/session occurred during self-administration. Animals were given 35 days to reach criterion. In Experiment 1, accelerated rates of acquisition of cocaine self-administration were evident for lead-exposed animals relative to controls. Overall, the number of self-administered cocaine infusions per session was significantly higher for lead-exposed rats as compared to control rats. Experiment 2 replicated Experiment 1 except that a higher dose of cocaine (0.80 mg/kg) was employed as the reinforcer, and 30 infusions/session was the set criterion. At the higher cocaine dose (Experiment 2), acquisition rates for control and lead-exposed animals were not markedly different, and significantly different infusion rates were not observed.
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http://dx.doi.org/10.1038/sj.npp.1300729DOI Listing
November 2005

The effects of the GABAA antagonist bicuculline on cocaine self-administration in rats exposed to lead during gestation/lactation.

Pharmacol Biochem Behav 2005 Apr;80(4):611-9

Department of Psychology, Texas A&M University, College Station, TX 77843, USA.

The present investigation examined the effects of perinatal lead exposure on cocaine self-administration following a GABAA antagonist pretreatment. Female rats were exposed to either 0 or 16 mg lead daily for 30 days prior to breeding with unexposed males. Beginning on postnatal day (PND) 75, control (N=10) and lead-exposed (N=8) animals were trained to self-administer 0.50 mg/kg cocaine intravenously (IV). After stable responding was established, animals were tested at 0.03 and 0.06 mg/kg cocaine delivered intravenously (IV), combined with intraperitoneal (IP) administration of either saline, 0.50, 1.00 or 2.00 mg/kg bicuculline (a GABAA antagonist). The results showed that control animals increased self-administration responding at a cocaine dose of 0.06 mg/kg as bicuculline dose increased. Lead-exposed animals exhibited an opposite pattern, i.e., a decrease in active (cocaine) lever responding occurred as the bicuculline dose was increased. Results at the 0.03 mg/kg cocaine dose failed to show group separation, or significant changes consequent to the bicuculline pretreatment. The data suggest that GABA antagonism results in increased reward potency of a low dose of cocaine and further, that this effect is differentially expressed in animals exposed to perinatal lead.
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http://dx.doi.org/10.1016/j.pbb.2005.01.011DOI Listing
April 2005

Exposure to cadmium during gestation and lactation decreases cocaine self-administration in rats.

Neurotoxicology 2004 Sep;25(5):869-75

Department of Psychology, Rm 230, Texas A&M University, College Station, TX 77843, USA.

This investigation examined the effects of perinatal cadmium exposure on subsequent self-administration of cocaine during the adult cycle. Female Sprague-Dawley rats were gavaged daily with 0.0 (14% sucrose solution, w/v) or 5.0 mg cadmium chloride (dissolved in 14% sucrose solution, w/v) for 30 days prior to breeding with non-exposed males. Dams continued to experience cadmium exposure through gestation and until pups were weaned at postnatal day (PND) 21. On PND 70, offspring were anesthetized and chronic indwelling jugular catheters were implanted. Following recovery, test subjects were trained in operant chambers to self-administer 0.500 mg/kg infusion (inf) intravenous cocaine on a fixed-ratio (FR) 2 schedule of reinforcement. Following acquisition, self-administration rates were tested for saline, 0.030, 0.060, 0.125, 0.250, and 0.500 mg/kg inf cocaine. Rats exposed developmentally to cadmium self-administered significantly less than controls at saline, 0.030, and 0.060 mg/kg inf cocaine. These data indicate that early-life cadmium exposure, a common exposure vector of which is the use of tobacco products, may affect cocaine sensitivity.
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http://dx.doi.org/10.1016/j.neuro.2004.01.001DOI Listing
September 2004

Self-administration of heroin in rats: effects of low-level lead exposure during gestation and lactation.

Psychopharmacology (Berl) 2004 Jul;174(2):203-10

Department of Psychology, Texas A&M University, College Station, TX 77843, USA.

Rationale: Developmental lead exposure has been found to produce differential patterns of drug self-administration in adult animals.

Objectives: The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult patterns of heroin self-administration.

Methods: Female rats were gavaged daily with 0 mg or 16 mg lead for 30 days prior to breeding with non-exposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning [postnatal day 21 (PND 21)]. Animals born to control or lead-exposed dams received indwelling jugular catheters as adults and were randomly assigned to one of two studies. In experiment 1, animals were tested on a FR-2 schedule in an effort to examine differential sensitivity to heroin in an intravenous self-administration paradigm. Seven doses of heroin were selected ranging from 0.56 microg/kg to 36 microg/kg per infusion. In experiment 2, littermates were tested on a progressive ratio (PR) schedule in order to more explicitly determine the nature of the change in sensitivity to the drug.

Results: In experiment 1, lead-exposed animals responded for heroin at significantly lower rates across most doses as evidenced by a downward shift in the inverted-U dose-effect curve. Congruent with these findings, lead-exposed animals in experiment 2 exhibited a decrease in progressive ratio responding (lower breaking points) across all heroin doses, further suggesting that perinatal lead exposure attenuates opiate self-administration in adult animals by altering the rewarding efficacy of the drug. In experiment 2, it was determined further that lead-exposed animals had lower latencies to make the initial lever press for heroin.

Conclusions: These results support previous literature suggesting that perinatal exposure to inorganic lead attenuates the effectiveness of opiates as a reinforcer when animals are tested in the adult life cycle.
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http://dx.doi.org/10.1007/s00213-003-1742-1DOI Listing
July 2004