578 results match your criteria hyperactivity dose-dependent


Ferulic acid alleviates abnormal behaviors in isolation-reared mice via 5-HT receptor partial agonist activity.

Psychopharmacology (Berl) 2021 Apr 8. Epub 2021 Apr 8.

Laboratory of Functional Biomolecules and Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan.

Rationale: Preclinical and clinical reports suggest that ferulic acid (FA), a plant-derived phenylpropanoid, is effective against mental health problems such as agitation, anxiety, and irritability in humans, without causing adverse side effects. However, the mechanism of action is unknown.

Objective: The aim of the study is to investigate the mechanism underlying the ameliorative effects of FA on mental health problems such as agitation, anxiety, and irritability, using in vivo behavioral analysis, in vitro pharmacological analysis, and in silico binding analysis. Read More

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The Use of Methylphenidate for Cognitive Enhancement in Young Healthy Adults: The Clinical and Ethical Debates.

J Clin Psychopharmacol 2021 Mar-Apr 01;41(2):100-102

Department of Health System Management, Ariel University, Ariel, Israel.

Objective: Methylphenidate (MP), a drug of choice for attention-deficit/hyperactivity disorder (ADHD), is a federally restricted substance CII in the United States because of abuse and dependence, and similar restrictions are practiced in Canada and around the world. This designation is given to drugs with medical value that present a high potential for abuse. In view of these severe restrictions, it is concerning to find out that a large group of healthy young adults, at least as large as the ADHD group of patients, take MP for cognitive enhancement, in an attempt to improve their academic achievements during studies and examinations. Read More

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Sodium salicylate enhances neural excitation via reducing GABAergic transmission in the dentate gyrus area of rat hippocampus in vivo.

Hippocampus 2021 May 13;31(5):512-521. Epub 2021 Feb 13.

Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.

Sodium salicylate, one of the non-steroidal anti-inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose-dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation. Read More

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Abstinence from chronic methylphenidate exposure modifies cannabinoid receptor 1 levels in the brain in a dose-dependent manner.

Curr Pharm Des 2021 Jan 27. Epub 2021 Jan 27.

Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, NY. United States.

Introduction: Methylphenidate (MP) is a widely used psychostimulant prescribed for Attention Deficit Hyperactivity Disorder, and is also used illicitly by healthy individuals. Chronic exposure to MP has been shown to affect physiology, behavior, and neurochemistry.

Methods: The present study examined its effect on the endocannabinoid system. Read More

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January 2021

The group II mGlu receptor antagonist LY341495 induces a rapid antidepressant-like effect and enhances the effect of ketamine in the chronic unpredictable mild stress model of depression in C57BL/6J mice.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Jan 2;109:110239. Epub 2021 Jan 2.

Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 31-343 Kraków, Smętna Street 12, Poland.

Ketamine produces a rapid antidepressant effect, but its use can be associated with serious side effects. Hence, other therapeutic options that will allow us to obtain a quick and safe antidepressant effect by modulating glutamatergic transmission are needed. Antagonists of mGlu2/3 receptors, which share some mechanisms of action with ketamine, may be good candidates to obtain this effect. Read More

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January 2021

Pharmacology, Dosing, and Side Effects of Rifabutin as a Possible Therapy for Antibiotic-Resistant Infections.

Open Forum Infect Dis 2020 Nov 15;7(11):ofaa460. Epub 2020 Oct 15.

Los Angeles County + University of Southern California Medical Center, Los Angeles, California, USA.

has among the highest rates of antibiotic resistance encountered in hospitals. New therapies are critically needed. We found that rifabutin has previously unrecognized hyperactivity against most strains of Here we review the pharmacology and adverse effects of rifabutin to inform potential oral dosing strategies in patients with infections. Read More

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November 2020

Psychosis-Like Behavior and Hyperdopaminergic Dysregulation in Human α-Synuclein BAC Transgenic Rats.

Mov Disord 2021 03 17;36(3):716-728. Epub 2020 Nov 17.

Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece.

Background: Parkinson's disease psychosis is a prevalent yet underreported and understudied nonmotor manifestation of Parkinson's disease and, arguably, the most debilitating. It is unknown if α-synuclein plays a role in psychosis, and if so, this endophenotype may be crucial for elucidating the neurodegenerative process.

Objectives: We sought to dissect the underlying neurobiology of novelty-induced hyperactivity, reminiscent of psychosis-like behavior, in human α-synuclein BAC rats. Read More

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A Post Hoc Comparison of Prior ADHD Medication Dose and Optimized Delayed-release and Extended-release Methylphenidate Dose in a Pivotal Phase III Trial.

Clin Ther 2020 12 7;42(12):2332-2340. Epub 2020 Nov 7.

Ironshore Pharmaceuticals & Development, Inc, Camana Bay, Grand Cayman, Cayman Islands.

Purpose: HLD200 is the first evening-dosed, delayed-release and extended-release methylphenidate (DR/ER-MPH) designed to delay initial release of MPH and provide treatment effects throughout the day and into the evening for individuals with attention-deficit/hyperactivity disorder (ADHD). Because DR/ER-MPH is uniquely absorbed in the colon, it cannot be substituted for other ADHD medications on a milligram-per-milligram basis. To provide clinicians with a target dose range for DR/ER-MPH when transitioning patients from a prior ADHD medication, dose conversion ratios (DCRs) between prior medication doses and optimized doses of DR/ER-MPH were determined post hoc from a pivotal Phase III study of children (aged 6-12 years) with ADHD. Read More

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December 2020

Oral Glucocorticoids and Incident Treatment of Diabetes Mellitus, Hypertension, and Venous Thromboembolism in Children.

Am J Epidemiol 2021 02;190(3):403-412

Rates of incident treatment were quantified in this study for diabetes mellitus, hypertension, and venous thromboembolism (VTE) associated with oral glucocorticoid exposure in children aged 1-18 years. The retrospective cohort included more than 930,000 children diagnosed with autoimmune diseases (namely, inflammatory bowel disease, juvenile idiopathic arthritis, or psoriasis) or a nonimmune comparator condition (attention-deficit/hyperactivity disorder) identified using US Medicaid claims (2000-2010). Associations of glucocorticoid dose per age- and sex-imputed weight with incident treated diabetes, hypertension, and VTE were estimated using Cox regression models. Read More

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February 2021

Functional ultrasound imaging to study brain dynamics: Application of pharmaco-fUS to atomoxetine.

Neuropharmacology 2020 11 13;179:108273. Epub 2020 Aug 13.

Theranexus, Lyon, France.

Functional ultrasound (fUS) is a new tool enabling the imaging of brain activity through the regional monitoring of cerebral blood volume (CBV) dynamics. This innovative technique has not yet demonstrated its full potential in pharmacological applications and drug development. In the current proof-of-concept study, the impact of atomoxetine (ATX), a potent norepinephrine reuptake inhibitor and non-stimulant treatment marketed in attention-deficit/hyperactivity-disorder, was evaluated in anesthetized rat using pharmacological functional ultrasound (pharmaco-fUS) at increasing doses (0. Read More

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November 2020

Is Methylphenidate Beneficial and Safe in Pharmacological Cognitive Enhancement?

Authors:
Ajay Kapur

CNS Drugs 2020 10;34(10):1045-1062

University of Oxford, Oxford, UK.

Nootropics are drugs used to either treat or benefit cognition deficits. Among this class, methylphenidate is a popular agent, which acts through indirect dopaminergic and noradrenergic agonism and, therefore, is proposed to enhance performance in catecholamine-dependent cognitive domains such as attention, memory and prefrontal cortex-dependent executive functions. However, investigation into the efficacy of methylphenidate as a cognitive enhancer has yielded variable results across all domains, leading to debate within the scientific community surrounding its off-label use in healthy individuals seeking scholaristic benefit or increased productivity. Read More

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October 2020

Nanoplastics impact the zebrafish (Danio rerio) transcriptome: Associated developmental and neurobehavioral consequences.

Environ Pollut 2020 Nov 16;266(Pt 2):115090. Epub 2020 Jul 16.

Institute of Environmental Health Sciences, Wayne State University, 6135 Woodward Ave, Detroit, MI, 48202, USA; Department of Pharmacology - School of Medicine, Wayne State University, 540 E Canfield, Detroit, MI, 28201, USA. Electronic address:

Microplastics (MPs) are a ubiquitous pollutant detected not only in marine and freshwater bodies, but also in tap and bottled water worldwide. While MPs have been extensively studied, the toxicity of their smaller counterpart, nanoplastics (NPs), is not well documented. Despite likely large-scale human and animal exposure to NPs, the associated health risks remain unclear, especially during early developmental stages. Read More

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November 2020

Antipsychotic-like effects of a novel phosphodiesterase 10A inhibitor MT-3014 in rats.

Pharmacol Biochem Behav 2020 09 18;196:172972. Epub 2020 Jun 18.

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.

Phosphodiesterase (PDE) 10A is an attractive therapeutic target for schizophrenia. Here, we investigated the antipsychotic-like effects of a novel PDE10A inhibitor, 1-({2-(7-fluoro-3-methylquinoxalin-2-yl)-5-[(3R)-3-fluoropyrrolidin-1-yl]pyrazolo[1,5-α]pyrimidin-7-yl}amino)-2-methylpropan-2-ol hydrochloride (MT-3014) in rats. MT-3014 showed a potent and selective inhibitory effect against PDE10A (IC = 0. Read More

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September 2020

Differential effects of alprazolam against methylphenidate-induced neurobehavioral alterations.

Physiol Behav 2020 08 12;222:112935. Epub 2020 May 12.

Institute of Forensic Sciences and Criminology, Panjab University, Chandigarh-160014, India. Electronic address:

Background: In the previous decade, abuse of several types of prescription drugs, particularly anxiolytics, opioid analgesics, and stimulants has increased significantly worldwide. Methylphenidate (MPH) and Alprazolam (ALZ) are extensively used drugs for the treatment of attention deficit hyperactivity disorder (ADHD) and anxiety disorders, respectively. However, these drugs have a high risk of being misused or abused alone, and their combination in some peculiar cases has shown their deleterious effects. Read More

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Drinking or smoking while breastfeeding and later developmental health outcomes in children.

BMC Res Notes 2020 Apr 26;13(1):232. Epub 2020 Apr 26.

Faculty of Medicine, Health and Human Sciences, Department of Psychology, Macquarie University, Sydney, Australia.

Objectives: Prenatal intake of alcohol and tobacco have been associated with negative outcomes in children. Consumption of alcohol while breastfeeding has also been associated with dose-dependent decreases in abstract reasoning ability and academic scores in children at later ages. Using longitudinal data from The Growing Up in Australia Study, the current study aimed to investigate whether intake of alcohol or tobacco while breastfeeding was related to later developmental health outcomes in children. Read More

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Gynecomastia: A Rare Adverse Effect of Methylphenidate in an Adolescent Boy.

Clin Psychopharmacol Neurosci 2020 May;18(2):337-339

Department of Child and Adolescent Psychiatry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.

Gynecomastia is a benign condition developing in association with localized fat deposition and glandular tissue proliferation in the breast in males, and characterized by breast growth. Drug is one of the most important factors in the etiology of gynecomastia. Methylphenidate is a commonly preferred and well-tolerated drug in the treatment of attention deficit hyperactivity disorder in children and adolescents. Read More

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Effects of safinamide on the glutamatergic striatal network in experimental Parkinson's disease.

Neuropharmacology 2020 06 3;170:108024. Epub 2020 Mar 3.

Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia, via Gambuli, 1, 06132, Perugia, Italy. Electronic address:

Objective: The aim of the study was to evaluate electrophysiological effects of safinamide on the intrinsic and synaptic properties of striatal spiny projection neurons (SPNs) and to characterize the possible therapeutic antiparkinsonian effect of this drug in dopamine (DA) denervated rats before and during levodopa (l-DOPA) treatment.

Background: Current therapeutic options in Parkinson's disease (PD) are primarily DA replacement strategies that usually cause progressive motor fluctuations and l-DOPA-induced dyskinesia (LIDs) as a consequence of SPNs glutamate-induced hyperactivity. As a reversible and use-dependent inhibitor of voltage-gated sodium channels, safinamide reduces the release of glutamate and possibly optimize the effect of l-DOPA therapy in PD. Read More

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Synthesis and biological investigation of triazolopyridinone derivatives as potential multireceptor atypical antipsychotics.

Bioorg Med Chem Lett 2020 04 19;30(8):127027. Epub 2020 Feb 19.

CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.

A series of triazolopyridinone derivatives originating from the antidepressant trazodone was designed and pharmacologically evaluated. Most of the compounds with a multireceptor functional profile exhibited high potency at the D, 5-HT, and 5-HT receptors. Compounds S1, S3, S9 and S12 were selected for further evaluation of druggable potential. Read More

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Scn8a Antisense Oligonucleotide Is Protective in Mouse Models of SCN8A Encephalopathy and Dravet Syndrome.

Ann Neurol 2020 03 6;87(3):339-346. Epub 2020 Feb 6.

Department of Human Genetics, University of Michigan, Ann Arbor, MI.

Objective: SCN8A encephalopathy is a developmental and epileptic encephalopathy (DEE) caused by de novo gain-of-function mutations of sodium channel Na 1.6 that result in neuronal hyperactivity. Affected individuals exhibit early onset drug-resistant seizures, developmental delay, and cognitive impairment. Read More

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Familial coaggregation of major psychiatric disorders among first-degree relatives of patients with obsessive-compulsive disorder: a nationwide study.

Psychol Med 2021 Mar 7;51(4):680-687. Epub 2020 Jan 7.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Whether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear.

Methods: Using the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD. Read More

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Rescue of PB-resistant neonatal seizures with single-dose of small-molecule TrkB antagonist show long-term benefits.

Epilepsy Res 2020 01 9;159:106249. Epub 2019 Dec 9.

Department of Neuroscience, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:

A recently characterized CD-1 mouse model of phenobarbital (PB)-resistant neonatal ischemic-seizures (i.e.; unilateral carotid ligation) was shown to be associated with age-dependent (P7 vs. Read More

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January 2020

Developmental toxicity of disinfection by-product monohaloacetamides in embryo-larval stage of zebrafish.

Ecotoxicol Environ Saf 2020 Feb 4;189:110037. Epub 2019 Dec 4.

Department of Public Health, Wuxi Center for Disease Control and Prevention, Wuxi, 214023, China. Electronic address:

As an emerging class of nitrogenous disinfection by-products (N-DBPs), haloacetamides (HAcAms) have been widely detected in drinking water. Limited toxicity studies have shown an inconsistent toxicity of monoHAcAms, including CAcAm, BAcAm and IAcAm. In this study, the developmental toxicity of monoHAcAms was evaluated in embryo-larval stage of zebrafish. Read More

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February 2020

Methylphenidate Dose-Dependently Affects Aggression and Improves Fear Extinction and Anxiety in BALB/cJ Mice.

Front Psychiatry 2019 25;10:768. Epub 2019 Oct 25.

Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboudumc, Nijmegen, Netherlands.

Overt aggression, increased anxiety, and dysfunctional fear processing are often observed in individuals with conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH), a psychostimulant increasing dopamine and noradrenaline tone, is effective in reducing aggression in both CD and ADHD individuals. However, it is unclear to which extent these effects of MPH are dose dependent. Read More

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October 2019

Propionic acid induced behavioural effects of relevance to autism spectrum disorder evaluated in the hole board test with rats.

Prog Neuropsychopharmacol Biol Psychiatry 2020 03 19;97:109794. Epub 2019 Oct 19.

The Kilee Patchell-Evans Autism Research Group, Department of Psychology, University of Western Ontario, London, Ontario, Canada; Department of Psychology, University of Western Ontario, London, Ontario, Canada; Graduate Program in Neuroscience, University of Western Ontario, London, Ontario, Canada. Electronic address:

Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterized by abnormal social interactions, impaired language, and stereotypic and repetitive behaviours. Among genetically susceptible subpopulations, gut and dietary influences may play a role in etiology. Propionic acid (PPA), produced by enteric gut bacteria, crosses both the gut-blood and the blood-brain barrier. Read More

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Effects of Developmental Nicotine Exposure on Frontal Cortical GABA-to-Non-GABA Neuron Ratio and Novelty-Seeking Behavior.

Cereb Cortex 2020 03;30(3):1830-1842

Center for Brain Repair, Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306-4300, USA.

Cigarette smoking during pregnancy is a major public health concern, resulting in detrimental health effects in the mother and her offspring. The adverse behavioral consequences for children include increased risk for attention deficit hyperactivity disorder, working memory deficits, epilepsy, novelty-seeking, and risk-taking behaviors. Some of these behavioral conditions are consistent with an imbalance in frontal cortical excitatory (glutamate) and inhibitory (GABA) neurotransmitter signaling. Read More

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Differential effects of d-amphetamine and atomoxetine on risk-based decision making of Lewis and Fischer 344 rats.

Behav Pharmacol 2019 10;30(7):605-616

Department of Psychology, West Virginia University, Morgantown, West Virginia, USA.

Individuals with attention-deficit/hyperactivity disorder tend to make risker choices during probabilistic-discounting procedures. Thus, how common attention-deficit/hyperactivity disorder medications affect probabilistic discounting is of interest. In general, d-amphetamine increases risk-taking while atomoxetine has produced mixed effects in rats. Read More

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October 2019

Sedative effects of the essential oil from the leaves of Lantana camara occurring in the Republic of Benin via inhalation in mice.

J Nat Med 2020 Jan 24;74(1):159-169. Epub 2019 Aug 24.

Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

Lantana camara Linn. (Verbenaceae) is used traditionally for its numerous medicinal properties such as antimalarial, antibacterial, anticancer and anti-inflammatory. In the present study, we investigated the chemical composition of essential oil from the leaves of L. Read More

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January 2020

Prenatal exposure to valproic acid is associated with altered neurocognitive function and neurogenesis in the dentate gyrus of male offspring rats.

Brain Res 2019 11 22;1723:146403. Epub 2019 Aug 22.

Department of Psychiatry, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 1138431, Japan. Electronic address:

In pregnant women with epilepsy, it is imperative to balance the safety of the mother and the potential teratogenicity of anticonvulsants, which could cause impairments such as intellectual disability and cleft lip. In this study, we examined behavioral and hippocampal neurogenesis alterations in male offspring of rats exposed to valproic acid (VPA) during pregnancy. Pregnant Wistar rats received daily intraperitoneal injections of VPA (100 mg/kg/day or 200 mg/kg/day) from embryonic day 12. Read More

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November 2019

Antipsychotic-like effects of a novel phosphodiesterase 10A inhibitor T-251 in rodents.

Pharmacol Biochem Behav 2019 10 9;185:172757. Epub 2019 Aug 9.

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.

Phosphodiesterase 10A (PDE10A) is a dual-substrate PDE that hydrolyzes both cAMP and cGMP. PDE10A is selectively expressed in medium spiny neurons in the striatum, suggesting the potential of PDE10A inhibitors in the treatment of schizophrenia. This study presents the pharmacological profile of a novel PDE10A inhibitor, 2-[(E)-2-(7-fluoro-3-methylquinoxalin-2-yl)vinyl]-6-pyrrolidin-1-yl-N-(tetrahydro-2H-pyran-4-yl)pyrimidin-4-amine hydrochloride (T-251) in rodent models of schizophrenia. Read More

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October 2019

Neurodevelopmental and Metabolomic Responses from Prenatal Coexposure to Perfluorooctanesulfonate (PFOS) and Methylmercury (MeHg) in Sprague-Dawley Rats.

Chem Res Toxicol 2019 08 8;32(8):1656-1669. Epub 2019 Aug 8.

Department of Laboratory Medicine and Pathology , University of Alberta , Edmonton , Alberta T6G 2G3 , Canada.

Methylmercury (MeHg) and perfluorooctanesulfonate (PFOS) are major contaminants of human blood that are both common in dietary fish, thereby raising questions about their combined impact on human development. Here, pregnant Sprague-Dawley rats ingested a daily dose, from gestational day 1 through to weaning, of either 1 mg/kg bw PFOS (PFOS-only), 1 mg/kg MeHg (MeHg-only), a mixture of 0.1 mg/kg PFOS and 1 mg/kg MeHg (Low-Mix), or of 1 mg/kg of PFOS and 1 mg/kg MeHg (High-Mix). Read More

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