385 results match your criteria amphetamine-induced hyperactivity


Analysis of morphological and neurochemical changes in subthalamic nucleus neurons in response to a unilateral 6-OHDA lesion of the substantia nigra in adult rats.

IBRO Neurosci Rep 2021 Jun 20;10:96-103. Epub 2021 Jan 20.

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia.

Background: Subthalamic nucleus (STN) neurons undergo changes in their pattern of activity and morphology during the clinical course of Parkinson's disease (PD). Striatal dopamine depletion and hyperactivity of neurons in the parafascicular nucleus (Pf) of the intralaminar thalamus are predicted to contribute to the STN changes.

Objective: This study investigated possible morphological and neurochemical changes in STN neurons in a rat model of unilateral, nigral dopamine neuron loss, in relation to previously documented alterations in Pf neurons. Read More

View Article and Full-Text PDF

Caenorhabditis elegans as an in vivo Model to Assess Amphetamine Tolerance.

Brain Behav Evol 2021 Apr 8:1-9. Epub 2021 Apr 8.

Department of Biology, Harriet L. Wilkes Honors College, Florida Atlantic University, Jupiter, Florida, USA.

Amphetamine is a potent psychostimulant also used to treat attention deficit/hyperactivity disorder and narcolepsy. In vivo and in vitro data have demonstrated that amphetamine increases the amount of extra synaptic dopamine by both inhibiting reuptake and promoting efflux of dopamine through the dopamine transporter. Previous studies have shown that chronic use of amphetamine causes tolerance to the drug. Read More

View Article and Full-Text PDF

Measuring Mania-like Elevated Mood through Amphetamine-induced 50-kHz Ultrasonic Vocalizations in Rats.

Authors:
Markus Wöhr

Br J Pharmacol 2021 Apr 8. Epub 2021 Apr 8.

KU Leuven, Faculty of Psychology and Educational Sciences, Research Unit Brain and Cognition, Laboratory of Biological Psychology, Social and Affective Neuroscience Research Group, B-3000, Leuven, Belgium.

Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by the psychostimulant d-amphetamine (AMPH). Exaggerated 50-kHz USV emission evoked by AMPH is modulated by dopamine, noradrenaline, and serotonin receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti-manic drug for treating bipolar disorder. Read More

View Article and Full-Text PDF

N-(3-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}propyl)-1H-indazole-3-carboxamide (D2AAK3) as a potential antipsychotic: In vitro, in silico and in vivo evaluation of a multi-target ligand.

Neurochem Int 2021 Jun 17;146:105016. Epub 2021 Mar 17.

Department of Pharmacology, Universidade de Santiago de Compostela, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Avda de Barcelona, E-15782, Santiago de Compostela, Spain.

Schizophrenia is a mental illness of not adequately understood causes that is not satisfactorily enough treated by current antipsychotics. In search for novel potential antipsychotics we performed structure-based virtual screening aimed to identify new dopamine D receptor antagonists. We found compound D2AAK3 with affinity to dopamine D receptor of 115 nM. Read More

View Article and Full-Text PDF

Regulation of GluA1 phosphorylation by d-amphetamine and methylphenidate in the cerebellum.

Addict Biol 2020 Dec 26:e12995. Epub 2020 Dec 26.

IGF, University of Montpellier, CNRS, Inserm, Montpellier, France.

Prescription stimulants, such as d-amphetamine or methylphenidate are used to treat suffering from attention-deficit hyperactivity disorder (ADHD). They potently release dopamine (DA) and norepinephrine (NE) and cause phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 in the striatum. Whether other brain regions are also affected remains elusive. Read More

View Article and Full-Text PDF
December 2020

ADHD-like behaviors caused by inactivation of a transcription factor controlling the balance of inhibitory and excitatory neuron development in the mouse anterior brainstem.

Transl Psychiatry 2020 10 21;10(1):357. Epub 2020 Oct 21.

Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, P.O. Box 56, 00014-University of Helsinki, Helsinki, Finland.

The neural circuits regulating motivation and movement include midbrain dopaminergic neurons and associated inhibitory GABAergic and excitatory glutamatergic neurons in the anterior brainstem. Differentiation of specific subtypes of GABAergic and glutamatergic neurons in the mouse embryonic brainstem is controlled by a transcription factor Tal1. This study characterizes the behavioral and neurochemical changes caused by the absence of Tal1 function. Read More

View Article and Full-Text PDF
October 2020

-(2-Hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1- benzimidazol-1-yl)propyl]piperidine-4-Carboxamide (D2AAK4), a Multi-Target Ligand of Aminergic GPCRs, as a Potential Antipsychotic.

Biomolecules 2020 02 24;10(2). Epub 2020 Feb 24.

Department of Pharmacology, Universidade de Santiago de Compostela, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Avda de Barcelona, E-15782 Santiago de Compostela, Spain.

-(2-hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1-benzimidazol -1-yl)propyl]piperidine-4-carboxamide (D2AAK4) is a multitarget ligand of aminergic G protein-coupled receptors (GPCRs) identified in structure-based virtual screening. Here we present detailed in vitro, in silico and in vivo investigations of this virtual hit. D2AAK4 has an atypical antipsychotic profile and low affinity to off-targets. Read More

View Article and Full-Text PDF
February 2020

Amphetamine-induced sensitization of hypertension and lamina terminalis neuroinflammation.

Am J Physiol Regul Integr Comp Physiol 2020 03 12;318(3):R649-R656. Epub 2020 Feb 12.

Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa.

Psychomotor stimulants are prescribed for many medical conditions, including obesity, sleep disorders, and attention-deficit/hyperactivity disorder. However, despite their acknowledged therapeutic utility, these stimulants are frequently abused, and their use can have both short- and long-term negative consequences. Although stimulants such as amphetamines acutely elevate blood pressure, it is unclear whether they cause any long-term effects on cardiovascular function after use has been discontinued. Read More

View Article and Full-Text PDF

Cerebral dopamine neurotrophic factor-deficiency leads to degeneration of enteric neurons and altered brain dopamine neuronal function in mice.

Neurobiol Dis 2020 02 26;134:104696. Epub 2019 Nov 26.

Institute of Biotechnology, HiLIFE Unit, Viikinkaari 5D, FI-00014, University of Helsinki, Finland.

Cerebral dopamine neurotrophic factor (CDNF) is neuroprotective for nigrostriatal dopamine neurons and restores dopaminergic function in animal models of Parkinson's disease (PD). To understand the role of CDNF in mammals, we generated CDNF knockout mice (Cdnf), which are viable, fertile, and have a normal life-span. Surprisingly, an age-dependent loss of enteric neurons occurs selectively in the submucosal but not in the myenteric plexus. Read More

View Article and Full-Text PDF
February 2020

Indoleamine-2,3-dioxygenase-1 is a molecular target for the protective activity of mood stabilizers against mania-like behavior induced by d-amphetamine.

Food Chem Toxicol 2020 Feb 21;136:110986. Epub 2019 Nov 21.

Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea. Electronic address:

It is recognized that d-amphetamine (AMPH)-induced hyperactivity is thought to be a valid animal model of mania. In the present study, we investigated whether a proinflammatory oxidative gene indoleamine-2,3-dioxygenase (IDO) is involved in AMPH-induced mitochondrial burden, and whether mood stabilizers (i.e. Read More

View Article and Full-Text PDF
February 2020

CK1δ over-expressing mice display ADHD-like behaviors, frontostriatal neuronal abnormalities and altered expressions of ADHD-candidate genes.

Mol Psychiatry 2020 12 19;25(12):3322-3336. Epub 2018 Oct 19.

Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.

The cognitive mechanisms underlying attention-deficit hyperactivity disorder (ADHD), a highly heritable disorder with an array of candidate genes and unclear genetic architecture, remain poorly understood. We previously demonstrated that mice overexpressing CK1δ (CK1δ OE) in the forebrain show hyperactivity and ADHD-like pharmacological responses to D-amphetamine. Here, we demonstrate that CK1δ OE mice exhibit impaired visual attention and a lack of D-amphetamine-induced place preference, indicating a disruption of the dopamine-dependent reward pathway. Read More

View Article and Full-Text PDF
December 2020

Questioning the predictive validity of the amphetamine-induced hyperactivity model for screening mood stabilizing drugs.

Authors:
Anat Lan Haim Einat

Behav Brain Res 2019 04 7;362:109-113. Epub 2019 Jan 7.

School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel; Dept. of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Israel; School of Pharmacy, University of Minnesota, United States. Electronic address:

Animal models are critical for the study of disease mechanisms and the screening of potential novel treatments. In the context of bipolar disorder, amphetamine-induced hyperactivity (AIH) is a frequently used screening model for antimanic effects. Yet, the utility of screening models depends on their predictive (or pharmacological) validity and it is expected that such models will respond to effective treatments. Read More

View Article and Full-Text PDF

The effects of amphetamine on working memory and locomotor activity in adult rats administered risperidone early in life.

Behav Brain Res 2019 04 27;362:64-70. Epub 2018 Dec 27.

Department of Psychological Science, Northern Kentucky University, Highland Heights, KY 41076, United States.

Antipsychotic drugs are used to manage symptoms of pediatric psychiatric disorders despite the relative absence of research regarding the long-term effects of these drugs on brain development. Using rats as a model, research has demonstrated that administration of the antipsychotic drug, risperidone, during early postnatal development elevates locomotor activity and sensitivity to the locomotor effects of amphetamine during adulthood. Because risperidone targets neurotransmitter receptors and forebrain regions associated with working memory, the present study determined whether early-life risperidone altered working memory during adulthood and its sensitivity to amphetamine-induced impairment. Read More

View Article and Full-Text PDF

Chronic methylphenidate treatment during adolescence has long-term effects on monoaminergic function.

J Psychopharmacol 2019 01 18;33(1):109-121. Epub 2018 Oct 18.

Pharmacology and Neuroscience Research Group, Leicester School of Pharmacy, De Montfort University, Leicester, UK.

Background: Psychostimulants like methylphenidate or D-amphetamine are often prescribed for attention deficit and hyperactivity disorders in children. Whether such drugs can be administered into a developing brain without consequences in adulthood is still an open question.

Methods: Here, using in vivo extracellular electrophysiology in anesthetised preparations, combined with behavioural assays, we have examined the long-term consequences in adulthood of a chronic methylphenidate oral administration (5 mg/kg/day, 15 days) in early adolescent (post-natal day 28) and late adolescent (post-natal day 42) rats, by evaluating body weight change, sucrose preference (indicator of anhedonia), locomotor sensitivity to D-amphetamine and electrical activities of ventral tegmental area dopamine and dorsal raphe nucleus serotonin neurons. Read More

View Article and Full-Text PDF
January 2019

ITGB4 deficiency in bronchial epithelial cells directs airway inflammation and bipolar disorder-related behavior.

J Neuroinflammation 2018 Aug 31;15(1):246. Epub 2018 Aug 31.

Department of Physiology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410007, People's Republic of China.

Background: Chronic persistent airway inflammation has been associated with the comorbidity of asthma and bipolar disorder (BD). However, the direct relevance between airway inflammation and BD-like psychiatric comorbidity is almost unknown. Integrin β4 (ITGB4) is downregulated on the airway epithelial of asthma patients, which might play a critical role in the parthenogenesis of airway inflammation. Read More

View Article and Full-Text PDF

Mutual activation of glutamatergic mGlu and muscarinic M receptors reverses schizophrenia-related changes in rodents.

Psychopharmacology (Berl) 2018 Oct 27;235(10):2897-2913. Epub 2018 Jul 27.

Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343, Kraków, Poland.

Rationale: Metabotropic glutamate receptors and muscarinic M receptors have been proposed as novel targets for various brain disorders, including schizophrenia. Both receptors are coupled to G proteins and are expressed in brain circuits that are important in schizophrenia. Therefore, their mutual activation may be an effective treatment and allow minimizing the doses of ligands required for optimal activity. Read More

View Article and Full-Text PDF
October 2018

GIT1 regulates synaptic structural plasticity underlying learning.

PLoS One 2018 19;13(3):e0194350. Epub 2018 Mar 19.

Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.

The signaling scaffold protein GIT1 is expressed widely throughout the brain, but its function in vivo remains elusive. Mice lacking GIT1 have been proposed as a model for attention deficit-hyperactivity disorder, due to alterations in basal locomotor activity as well as paradoxical locomotor suppression by the psychostimulant amphetamine. Since we had previously shown that GIT1-knockout mice have normal locomotor activity, here we examined GIT1-deficient mice for ADHD-like behavior in more detail, and find neither hyperactivity nor amphetamine-induced locomotor suppression. Read More

View Article and Full-Text PDF

Glutamate Dehydrogenase-Deficient Mice Display Schizophrenia-Like Behavioral Abnormalities and CA1-Specific Hippocampal Dysfunction.

Schizophr Bull 2019 01;45(1):127-137

Department of Psychology or Neurobiology, University of Haifa, Haifa, Israel.

Brain imaging has revealed that the CA1 subregion of the hippocampus is hyperactive in prodromal and diagnosed patients with schizophrenia (SCZ), and that glutamate is a driver of this hyperactivity. Strikingly, mice deficient in the glutamate synthetic enzyme glutaminase have CA1 hypoactivity and a SCZ-resilience profile, implicating glutamate-metabolizing enzymes. To address this further, we examined mice with a brain-wide deficit in the glutamate-metabolizing enzyme glutamate dehydrogenase (GDH), encoded by Glud1, which should lead to glutamate excess due to reduced glutamate metabolism in astrocytes. Read More

View Article and Full-Text PDF
January 2019

Interference of norepinephrine transporter trafficking motif attenuates amphetamine-induced locomotor hyperactivity and conditioned place preference.

Neuropharmacology 2018 Jan 4;128:132-141. Epub 2017 Oct 4.

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address:

Amphetamine (AMPH)-mediated norepinephrine transporter (NET) downregulation requires NET-T258/S259 trafficking motif. The present study utilizes cell permeable NET-T258/S259 motif interfering peptide, which blocks AMPH-induced NET downregulation, to explore the role of this form of NET regulation in AMPH-mediated behaviors. In rats receiving intra-accumbal microinjections of TAT-conjugated peptides encompassing NET-T258/S259 motif, acute systemic AMPH failed to inhibit NE transport in the TAT-NET-T258/S259 wild-type (WT) peptide injected hemisphere but not in the vehicle or scrambled peptide injected hemisphere. Read More

View Article and Full-Text PDF
January 2018

Differential Associations between Cortical Thickness and Striatal Dopamine in Treatment-Naïve Adults with ADHD vs. Healthy Controls.

Front Hum Neurosci 2017 22;11:421. Epub 2017 Aug 22.

Department of Neurology and Neurosurgery, McGill UniversityMontréal, QC, Canada.

Alterations in catecholamine signaling and cortical morphology have both been implicated in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). However, possible links between the two remain unstudied. Here, we report exploratory analyses of cortical thickness and its relation to striatal dopamine transmission in treatment-naïve adults with ADHD and matched healthy controls. Read More

View Article and Full-Text PDF

Antimanic Efficacy of a Novel Kv3 Potassium Channel Modulator.

Neuropsychopharmacology 2018 Jan 31;43(2):435-444. Epub 2017 Aug 31.

Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Kv3.1 and Kv3.2 voltage-gated potassium channels are expressed on parvalbumin-positive GABAergic interneurons in corticolimbic brain regions and contribute to high-frequency neural firing. Read More

View Article and Full-Text PDF
January 2018

Potential role of tyrosine hydroxylase in the loss of psychostimulant effect of amphetamine under conditions of impaired dopamine transporter activity.

Behav Brain Res 2017 09 24;334:105-108. Epub 2017 Jul 24.

Neuroscience Research, AbbVie, Ludwigshafen, Germany.

Amphetamine and methylphenidate are known to have stimulatory effect in healthy subjects but not in humans with attention deficit hyperactivity disorder and in rodents with impaired dopamine transporter (DAT) function. This phenomenon is called the paradoxical calming effect of psychostimulants. It has been previously demonstrated that psychostimulants may regulate the enzymatic activity of tyrosine hydroxylase (TH). Read More

View Article and Full-Text PDF
September 2017

Selective enhancement of NMDA receptor-mediated locomotor hyperactivity by male sex hormones in mice.

Psychopharmacology (Berl) 2017 Sep 3;234(18):2727-2735. Epub 2017 Jul 3.

Mental Health Research Institute, Parkville, VIC, Australia.

Rationale: Altered glutamate NMDA receptor function is implicated in schizophrenia, and gender differences have been demonstrated in this illness.

Objectives: This study aimed to investigate the interaction of gonadal hormones with NMDA receptor-mediated locomotor hyperactivity and PPI disruption in mice.

Results: The effect of 0. Read More

View Article and Full-Text PDF
September 2017

Discovery of N-Substituted (2-Phenylcyclopropyl)methylamines as Functionally Selective Serotonin 2C Receptor Agonists for Potential Use as Antipsychotic Medications.

J Med Chem 2017 07 18;60(14):6273-6288. Epub 2017 Jul 18.

Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago , Chicago, Illinois 60612, United States.

A series of N-substituted (2-phenylcyclopropyl)methylamines were designed and synthesized, with the aim of finding serotonin 2C (5-HT)-selective agonists with a preference for G signaling. A number of these compounds exhibit 5-HT selectivity with a preference for G-mediated signaling compared with β-arrestin recruitment. Furthermore, the N-methyl compound (+)-15a, which displayed an EC of 23 nM in the calcium flux assay while showing no β-arrestin recruitment activity, is the most functionally selective 5-HT agonist reported to date. Read More

View Article and Full-Text PDF

Treatment with levetiracetam improves cognition in a ketamine rat model of schizophrenia.

Schizophr Res 2018 03 17;193:119-125. Epub 2017 Jun 17.

Department of Psychological and Brain Sciences, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; AgeneBio, Inc., 1101 E. 33rd Street, Suite C310, Baltimore, MD 21218, USA.

Imbalance in neural excitation and inhibition is associated with behavioral dysfunction in individuals with schizophrenia and at risk for this illness. We examined whether targeting increased neural activity with the antiepileptic agent, levetiracetam, would benefit memory performance in a preclinical model of schizophrenia that has been shown to exhibit hyperactivity in the hippocampus. Adult rats exposed to ketamine subchronically during late adolescence showed impaired hippocampal-dependent memory performance. Read More

View Article and Full-Text PDF

RP5063, an atypical antipsychotic drug with a unique pharmacologic profile, improves declarative memory and psychosis in mouse models of schizophrenia.

Behav Brain Res 2017 08 31;332:180-199. Epub 2017 Mar 31.

Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address:

Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D, D, D, serotonin (5-HT), and 5-HT receptors (Rs), full agonism at αβ nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT, 5-HT, and 5-HTRs. Most atypical APDs are 5-HT inverse agonists. Read More

View Article and Full-Text PDF

Sex differences in psychotomimetic-induced behaviours in rats.

Behav Brain Res 2017 03 19;322(Pt A):157-166. Epub 2017 Jan 19.

Behavioural Neuroscience Laboratory, Mental Health Research Institute, Parkville, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, Australia.

Animal model studies using equal numbers of males and females are sparse in psychiatry research. Given the marked sex differences observed in psychiatric disorders, such as schizophrenia, using both males and females in research studies is an important requirement. Thus the aim of this study was to examine sex differences in psychotomimetic-induced behavioural deficits relevant to psychosis. Read More

View Article and Full-Text PDF

RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network ("Rhesactome") in the striatum.

Sci Signal 2016 11 15;9(454):ra111. Epub 2016 Nov 15.

Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA.

The striatum of the brain coordinates motor function. Dopamine-related drugs may be therapeutic to patients with striatal neurodegeneration, such as Huntington's disease (HD) and Parkinson's disease (PD), but these drugs have unwanted side effects. In addition to stimulating the release of norepinephrine, amphetamines, which are used for narcolepsy and attention-deficit/hyperactivity disorder (ADHD), trigger dopamine release in the striatum. Read More

View Article and Full-Text PDF
November 2016

Differential roles for cortical versus sub-cortical noradrenaline and modulation of impulsivity in the rat.

Psychopharmacology (Berl) 2017 Jan 15;234(2):255-266. Epub 2016 Oct 15.

School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK.

Rationale: Atomoxetine is a noradrenaline re-uptake inhibitor licensed for the treatment of adult and childhood attention deficit hyperactivity disorder. Although atomoxetine has established efficacy, the mechanisms which mediate its effects are not well understood.

Objectives: In this study, we investigated the role of cortical versus sub-cortical noradrenaline by using focal dopamine beta hydroxylase-saporin-induced lesions, to the prefrontal cortex (n = 16) or nucleus accumbens shell (n = 18). Read More

View Article and Full-Text PDF
January 2017

Locomotor Profiling from Rodents to the Clinic and Back Again.

Curr Top Behav Neurosci 2016;28:287-303

Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA, 92093-0804, USA.

The quantification of unconditioned motoric activity is one of the oldest and most commonly utilized tools in behavioral studies. Although typically measured in reference to psychiatric disorders, e.g. Read More

View Article and Full-Text PDF
December 2016