Chlorpromazine as a discriminative stimulus in rats: Generalization to typical and atypical antipsychotics

The discriminative stimulus properties of the typical antipsychotic chlorpr omazine were examined in a two-lever drug discrimination procedure for food reward. Six of nine rats readily acquired the discrimination between 1.0 m g/kg chlorpromazine (i.p.) and vehicle in a mean of 29.7 training sessions. The chlorpromazine generalization curve was dose-dependent and yielded an ED50 of 0.305 mg/kg (95% confidence interval (CI) = 0.201-0.463 mg/kg). The chlorpromazine cue generalized to the atypical antipsychotics clozapine (E D50 for the clozapine curve was 0.258 mg/kg [95% CI = 0.047-1.420 mg/kg]) a nd olanzapine (ED50 for the olanzapine curve was 0.199 mg/kg [95% CI = 0.07 6-0.522 mg/kg]) and to the typical antipsychotic thioridazine (ED50 for the thioridazine curve was 3.103 mg/kg [95% CI = 1.993-4.832 mg/kg]). Haloperi dol (a typical antipsychotic) and raclopride (an atypical antipsychotic) di d not substitute for chlorpromazine. It is clear from the present results t hat the discriminative stimulus properties of chlorpromazine share similari ties both with the atypical antipsychotics clozapine and olanzapine and wit h the typical antipsychotic thioridazine. The extent to which the discrimin ative stimulus properties of antipsychotic drugs reflect or are predictive of their therapeutic effects in schizophrenic patients remains unclear. Dru g Dev. Res. 48:38-44, 1999. (C) 1999 Wiley-Liss, Inc.