Availability of N-Methyl-d-Aspartate Receptor Coagonists Affects Cocaine-Induced Conditioned Place Preference and Locomotor Sensitization: Implications for Comorbid Schizophrenia and Substance Abuse

The Journal of Pharmacology and Experimental Therapeutics
Matthew D PuhlJoseph T Coyle

Abstract

Schizophrenia is associated with high prevalence of substance abuse. Recent research suggests that dysregulation of N-methyl-d-aspartate receptor (NMDAR) function may play a role in the pathophysiology of both schizophrenia and drug addiction, and thus, may account for this high comorbidity. Our laboratory has developed two transgenic mouse lines that exhibit contrasting NMDAR activity based on the availability of the glycine modulatory site (GMS) agonists d-serine and glycine. Glycine transporter 1 knockdowns (GlyT1(+/-)) exhibit NMDAR hyperfunction, whereas serine racemase knockouts (SR(-/-)) exhibit NMDAR hypofunction. We characterized the behavior of these lines in a cocaine-induced (20 mg/kg) conditioned place preference (CPP) and locomotor sensitization paradigm. Compared with wild-type mice, GlyT1(+/-) mice displayed hastened extinction of CPP and robust cocaine-induced reinstatement. SR(-/-) mice appeared to immediately "forget" the learned preference, because they did not exhibit cocaine-induced reinstatement and also displayed attenuated locomotor sensitization. Treatment of GlyT1(+/-) mice with gavestinel (10 mg/kg on day 1; 5 mg/kg on days 2-17), a GMS antagonist, attenuated cocaine-induced CPP and caused them to im...Continue Reading

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Citations

Feb 3, 2016·Journal of Pharmacological and Toxicological Methods·Sarah-Lena PuhlMetin Avkiran
Mar 24, 2016·Brain Research Bulletin·Dr Patricia McLaughlin
Apr 3, 2016·Behavioural Brain Research·J Andrew HardawayThomas L Kash
Apr 28, 2017·Molecular Brain·James MaksymetzP Jeffrey Conn
May 24, 2020·Cellular and Molecular Neurobiology·Shunsuke TakagiJoseph T Coyle
Dec 2, 2020·The American Journal of Psychiatry·Joseph T CoyleDarrick T Balu
Jul 28, 2020·Neuroscience and Biobehavioral Reviews·Bruno Lemes MarquesMauro Cunha Xavier Pinto

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