Dissimilar effects of subchronic clozapine and haloperidol on operant lever pressing in C57BL/6J, BALB/cJ, and LP/J mice

Abstract

The effects of the atypical antipsychotic, clozapine, and the typical antipsychotic, haloperidol, on operant behavior have been well described in the rat; however, little such work has been done with mice. In the present study, the effects of clozapine (2.0, 4.0, and 6.0 mg/kg) and haloperidol (0.06, 0.13, and 0.25 mg/kg) were evaluated in three inbred strains of mice (C57BL/6J, BALB/cJ, and LP/J mice) across six consecutive daily sessions at each dose, in which each lever press produced access to milk. Tolerance to the rate-reducing effects of clozapine was observed in the BALB/cJ strain, but not in the C57BL/6J and LP/J strains. In contrast, sensitization was observed in the three mouse strains treated with subchronic haloperidol. These results are at odds with the operant rat literature on the effects of clozapine, but are consistent with the idea that genetic variables contribute, at least in part, to some of the differences observed in response to antipsychotics.