Characterization of the discriminative stimulus properties of the atypical antipsychotic amisulpride in C57BL/6 mice

Abstract

CHARACTERIZATION OF THE DISCRIMINATIVE STIMULUS PROPERTIES OF THE ATYPICAL ANTIPSYCHOTIC AMISULPRIDE IN C57BL/6 MICE By Timothy John Donahue, MS, MA, M.Ed. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2014 Major Director Joseph H. Porter, Ph.D. Professor, Department of Psychology Amisulpride, a benzamide derivative, is a second generation (atypical) antipsychotic drug used to treat both positive and negative symptoms of schizophrenia. Amisulpride is a relatively selective antagonist at dopamine D2 and D3 receptors and at serotonin 5-HT2B and 5-HT7 receptors. This is a unique binding profile as compared to both first generation (typical) and second generation antipsychotic drugs. It is approved in Europe and displays an atypical clinical profile with reduced extrapyramidal motor effects. The drug has a chiral center and is a mixture of two optical isomers: (S)-amisulpride and (R)-amisulpride. The therapeutic form of the drug is a mixture of these two enantiomers (rac-amisulpride). The present study used a two-lever drug discrimination assay to allow a direct comparison between amisulpride and its two isomers. Additionally, substitution testing was conducted with the typical antipsychotics haloperidol and chlorpromazine; the atypical antipsychotics olanzapine, clozapine, risperidone, quetiapine and aripiprazole; the antidepressants imipramine, fluoxetine, bupropion, mianserin; the anxiolytic