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Chlorpromazine as a discriminative stimulus in rats: Generalization to typical and atypical antipsychotics
Author(s) -
Porter Joseph H.,
Covington Herbert E.,
Varvel Stephen A.,
Vann Robert E.,
Warren Tracy A.
Publication year - 1999
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199909)48:1<38::aid-ddr5>3.0.co;2-c
Subject(s) - chlorpromazine , olanzapine , thioridazine , antipsychotic , clozapine , haloperidol , atypical antipsychotic , typical antipsychotic , ed50 , pharmacology , psychology , dopamine antagonist , medicine , psychiatry , schizophrenia (object oriented programming) , dopamine , receptor
The discriminative stimulus properties of the typical antipsychotic chlorpromazine were examined in a two‐lever drug discrimination procedure for food reward. Six of nine rats readily acquired the discrimination between 1.0 mg/kg chlorpromazine (i.p.) and vehicle in a mean of 29.7 training sessions. The chlorpromazine generalization curve was dose‐dependent and yielded an ED 50 of 0.305 mg/kg (95% confidence interval (CI) = 0.201–0.463 mg/kg). The chlorpromazine cue generalized to the atypical antipsychotics clozapine (ED 50 for the clozapine curve was 0.258 mg/kg [95% CI = 0.047–1.420 mg/kg]) and olanzapine (ED 50 for the olanzapine curve was 0.199 mg/kg [95% CI = 0.076–0.522 mg/kg]) and to the typical antipsychotic thioridazine (ED 50 for the thioridazine curve was 3.103 mg/kg [95% CI = 1.993–4.832 mg/kg]). Haloperidol (a typical antipsychotic) and raclopride (an atypical antipsychotic) did not substitute for chlorpromazine. It is clear from the present results that the discriminative stimulus properties of chlorpromazine share similarities both with the atypical antipsychotics clozapine and olanzapine and with the typical antipsychotic thioridazine. The extent to which the discriminative stimulus properties of antipsychotic drugs reflect or are predictive of their therapeutic effects in schizophrenic patients remains unclear. Drug Dev. Res. 48:38–44, 1999. © 1999 Wiley‐Liss, Inc.