Impact of mGluR5 during amphetamine-induced hyperactivity and conditioned hyperactivity in differentially reared rats

Abstract

3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTEP) is a metabotropic glutamate receptor 5 (mGluR5) antagonist that may alter drug sensitivity in differentially reared rats due to its involvement in the psychostimulant reward pathway and plasticity. The purpose of this study was to assess the effects of MTEP on acute amphetamine-induced hyperactivity, conditioned hyperactivity, and sensitization. Rats were reared in an enriched (EC), isolated (IC), or standard (SC) condition after which rats were either administered MTEP (1.0mg/kg, ip) or saline prior to an acute (0.5 or 1.0mg/kg, sc) or repeated (0.3mg/kg, sc) amphetamine exposure. Rats undergoing repeated amphetamine exposure were administered MTEP prior to conditioned hyperactivity and sensitization tests. EC and SC rats administered with MTEP prior to acute amphetamine demonstrated attenuated amphetamine-induced locomotor activity compared to controls, while IC rats administered MTEP following repeated amphetamine exposure demonstrated attenuated amphetamine-induced locomotor activity. Interestingly, MTEP treatment only altered conditioned hyperactivity in EC rats, as MTEP pretreatment resulted in conditioned hyperactivity in EC rats while conditioned hyperactivity was not observed in EC rats pretreated with saline. Glutamatergic pathways are altered during differential rearing, which differentially alters the role of mGluR5 in EC, IC, and SC rats when administered psychostimulant acutely versus repeatedly. These findings suggest that differential rearing alters glutamatergic function, which reduces sensitivity to psychostimulants.