ESTABLISHING THE DISCRIMINATIVE STIMULUS PROPERTIES OF THE ATYPICAL ANTIPSYCHOTIC AMISULPRIDE IN C57BL/6 MICE

摘要

Abstract ESTABLISHING THE DISCRIMINATIVE STIMULUS PROPERTIES OF THE ATYPICAL ANTIPSYCHOTIC AMISULPRIDE IN C57BL/6 MICE Antipsychotic medications are used to treat schizophrenia. The present study used the drug discrimination paradigm to measure the subjective effects of the atypical antipsychotic amisulpride and to examine the underlying neuropharmacological mechanisms responsible for the discriminative stimulus property of the drug. Male C57BL/6 mice were trained to discriminate 10 mg/kg (-)S amisulpride from vehicle in a two-lever drug discrimination task. A dose effect curve for (-)S amisulpride yielded an ED50 = 1.77 mg/kg 95% CI [1.28, 2.45 mg/kg]. Substitution testing was conducted for the isomer (+)R amisulpride, racemic (±)SR amisulpride, the atypical antipsychotics clozapine, aripiprazole and the typical antipsychotic haloperidol. There was partial substitution for (+)R amisulpride, and full substitution for (±)SR amisulpride with a significant rightward shift in the dose effect curves. Clozapine, aripiprazole, and haloperidol failed to fully substitute with significant rate suppression at the higher doses. These results demonstrated that (-)S amisulpride has a unique discriminative stimulus that differs from other antipsychotic drugs.