title: (S)-amisulpride as a discriminative stimulus in C57BL/6 mice and its comparison to the stimulus effects of typical and atypical antipsychotics.
abstract: Amisulpride, a substituted benzamide derivative, exerts atypical antipsychotic and antidepressant clinical effects and its (S)-stereoisomer is thought to underlie these actions. In the present study, male C57BL/6 mice were trained to discriminate (S)-amisulpride (10mg/kg, s.c.) from vehicle in a two-lever drug discrimination task for food reward. The (S)-amisulpride stimulus was rapidly acquired and was shown to be dose-related, time dependent (effective between 30 and 120min) and stereoselective: (S)-amisulpride (ED50=1.77mg/kg; 4.2µmol/kg) was about three times more potent than rac-amisulpride (ED50=4.94mg/kg; 13.4µmol/kg) and ten times more potent than (R)-amisulpride (ED50=15.84mg/kg; 42.9µmol/kg). In tests of stimulus generalization, the (S)-amisulpride stimulus generalized completely to sulpiride (ED50=12.67mg/kg; 37.1µmol/kg), a benzamide analog that also is purported to be an atypical antipsychotic, but did not fully generalize to the typical antipsychotic drug haloperidol (maximum of 45% drug-lever responding) nor to the atypical antipsychotic drugs clozapine (partial substitution of 65% drug-lever responding) or aripiprazole (~30% drug-lever responding). These results demonstrated that (S)-amisulpride appears to exert a unique discriminative stimulus effect that is similar to other benzamides, but which differs from other structural classes of antipsychotic drugs.
authors.affiliation: Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Donahue
authors.affiliation: Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Hillhouse
authors.affiliation: Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Webster
authors.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Young
authors.affiliation: Center for Drug Discovery, Georgetown University, Washington, DC, USA.
authors.forename: Eliseu O
authors.initials: EO
authors.lastname: De Oliveira
authors.affiliation: Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: jporter@vcu.edu.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Porter
mesh_terms: D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012201:Reward; D013237:Stereoisomerism; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D013469:Sulpiride; D000077582:Amisulpride
keywords: Amisulpride; Antipsychotic drugs; Benzamides; C57BL/6 mice; Drug discrimination; Schizophrenia