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- Title
Discriminative stimulus properties of the atypical antipsychotic amisulpride: comparison to its isomers and to other benzamide derivatives, antipsychotic, antidepressant, and antianxiety drugs in C57BL/6 mice.
- Authors
Donahue, Timothy; Hillhouse, Todd; Webster, Kevin; Young, Richard; Oliveira, Eliseu; Porter, Joseph
- Abstract
Rationale: Racemic ( RS)-amisulpride (Solian) is an atypical antipsychotic drug used to treat schizophrenia and dysthymia. Blockade of dopamine D/D and/or serotonin 5-HT receptors is implicated in its pharmacological effects. While the ( S)-amisulpride isomer possesses a robust discriminative cue, discriminative stimulus properties of ( RS)-amisulpride have not been evaluated. Objectives: The present study established ( RS)-amisulpride as a discriminative stimulus and assessed amisulpride-like effects of amisulpride stereoisomers, other benzamide derivatives, and antipsychotic, antidepressant, and anxiolytic drugs. Methods: Adult, male C57BL/6 mice were trained to discriminate 10 mg/kg ( RS)-amisulpride from vehicle in a two-lever food-reinforced operant conditioning task. Results: ( RS)-Amisulpride's discriminative stimulus was dose-related, time-dependent, and stereoselective. ( S)-Amisulpride (an effective dose of 50% (ED) = 0.21 mg/kg) was three times more potent than ( RS)-amisulpride (ED = 0.60 mg/kg) or ( R)-amisulpride (ED = 0.68 mg/kg). ( RS)-Amisulpride generalized fully to the structurally related atypical antipsychotic/antidysthymia drug sulpiride (Sulpor; ED = 7.29 mg/kg) and its ( S)-enantiomer (ED = 9.12 mg/kg); moderate to high partial generalization [60-75% drug lever responding (%DLR)] occurred to the benzamide analogs tiapride (Tiapridal) and raclopride, but less than 60% DLR to metoclopramide (Reglan), nemonapride (Emilace), and zacopride. Antipsychotic, antidepressant, and antianxiety drugs from other chemical classes (chlorpromazine, quetiapine, risperidone, and mianserin) produced 35-55% amisulpride lever responding. Lastly, less than 35% DLR occurred for clozapine, olanzapine, aripiprazole imipramine, chlordiazepoxide, and bupropion. Conclusions: ( RS)-Amisulpride generalized to some, but not all benzamide derivatives, and it failed to generalize to any other antipsychotic, antidepressant, or antianxiety drugs tested. Interestingly, the ( R)-isomer shared very strong stimulus properties with ( RS)-amisulpride. This finding was in contrast to findings from Donahue et al. ( Eur J Pharmacol 734:15-22, 2014), which found that the ( R)-isomer did not share very strong stimulus properties when the ( S)-isomer was the training drug.
- Subjects
RACEMIC mixtures; AMISULPRIDE; ANTIPSYCHOTIC agents; SCHIZOPHRENIA treatment; DYSTHYMIC disorder; BENZAMIDE
- Publication
Psychopharmacology, 2017, Vol 234, Issue 23/24, p3507
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-017-4738-y