The effect of chronic treatment with clozapine and haloperidol on stimulus control by DOM

The present study investigated the effects of chronic treatment with the atypical antipsychotic, clozapine, or the typical antipsychotic, haloperidol, on the stimulus properties of 2,5-dimethoxy-4-methylamphetamine ([-]-DOM) in rats trained to discriminate [-]-DOM (0.3 mg/kg; 75 min pre-treatment time) from vehicle. As compared with control values, treatment with clozapine (25 mg/kg.d) for 7 d caused a statistically significant 57% reduction in [-]-DOM-appropriate responding. Unlike clozapine, treatment with haloperidol (1 mg/kg.d) for 7 d did not affect the stimulus properties of [-]-DOM. These findings demonstrate that a functionally significant decrease in 5-HT_2A receptor-mediated activity is a unique component of the in-vivo response to chronic treatment with clozapine but not haloperidol and, therefore, might account for some of the clinical differences associated with atypical antipsychotics.