Effects of typical, atypical, and novel antipsychotic drugs on amphetamine-induced place conditioning in rats

Because amphetamine-induced place conditioning is believed to be mediated by dopamine (DA) receptors within the nucleus accumbens, this behavioral model may be useful for detecting drugs with antipsychotic efficacy. To test the selectivity and specificity of the model, the present study examined whether amphetamine-induced place conditioning is reversible in rats pretreated with the classical antipsychotic haloperidol, the atypical antipsychotic clozapine, and the novel antipsychotics raclopride and risperidone. The non-antipsychotic drugs baclofen and prazosin were also tested. Male Sprague-Dawley rats received d-amphetamine (5.4 mu mol/kg ip) paired with one side of a two-compartment box and saline paired with the other side. During these pairings, locomotor activity was measured. On the test day, the amount of time drug-free rats spent in each compartment was determined. Rats trained with amphetamine alone showed a significant increase in time spent on the drug-paired side from pre- to postconditioning, indicating a place preference. Pretreatment with the highest dose of either haloperidol (0.026, 0.13, 0.26 mu mol/kg sc), clozapine (3, 15, 30, 60 mu mol/kg sc), raclopride (0.1, 0.2, 1.0 mu mol/kg), or risperidone (0.12, 0.24, 1.2 mu mol/kg sc) prior to amphetamine significantly blocked the establishment of place conditioning. Treatment with the antipsychotic alone did not support place conditioning (preference or aversion). On conditioning days, haloperidol, clozapine, raclopride, and risperidone significantly decreased amphetamine-induced locomotor activity. Pretreatment with either baclofen or prazosin failed to disrupt amphetamine-induced place conditioning despite significant decreases in locomotor activity on the conditioning days. These data provide preliminary support for amphetamine place conditioning as a rodent model for detecting drugs with antipsychotic efficacy. (C) 1995 Wiley-Liss, Inc.