EFFECTS OF TYPICAL, ATYPICAL, AND NOVEL ANTIPSYCHOTIC-DRUGS ON AMPHETAMINE-INDUCED PLACE CONDITIONING IN RATS

Because amphetamine-induced place conditioning is believed to be media ted by dopamine (DA) receptors within the nucleus accumbens, this beha vioral model may be useful for detecting drugs with antipsychotic effi cacy. To test the selectivity and specificity of the model, the presen t study examined whether amphetamine-induced place conditioning is rev ersible in rats pretreated with the classical antipsychotic haloperido l, the atypical antipsychotic clozapine, and the novel antipsychotics raclopride and risperidone. The non-antipsychotic drugs baclofen and p razosin were also tested. Male Sprague-Dawley rats received d-amphetam ine (5.4 mu mol/kg ip) paired with one side of a two-compartment box a nd 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 amphe tamine alone showed a significant increase in time spent on the drug-p aired side from pre- to postconditioning, indicating a place preferenc e. 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), raclop ride (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 o f place conditioning. Treatment with the antipsychotic alone did not s upport place conditioning (preference or aversion). On conditioning da ys, haloperidol, clozapine, raclopride, and risperidone significantly decreased amphetamine-induced locomotor activity. Pretreatment with ei ther baclofen or prazosin failed to disrupt amphetamine-induced place conditioning despite significant decreases in locomotor activity on th e conditioning days. These data provide preliminary support for amphet amine place conditioning as a rodent model for detecting drugs with an tipsychotic efficacy. (C) 1995 Wiley-Liss, Inc.