Low-dose clozapine pretreatment partially prevents haloperidol-induced deficits in conditioned active avoidance

The effectiveness of neuroleptics in disrupting conditioned active avoidanc e has led to the widespread use of this test as an index of antipsychotic e fficacy, whereas the tendency for these drugs to induce catalepsy is believ ed to reflect their propensity to cause extrapyramidal motor side-effects. Although the typical neuroleptic haloperidol produces catalepsy as well as profound deficits in conditioned active avoidance, the atypical neuroleptic clozapine does not induce catalepsy and is less effective than haloperidol in disrupting active avoidance. Furthermore, clozapine pretreatment preven ts haloperidol-induced catalepsy. We investigated whether clozapine pretrea tment might also reduce the disruptive effects of haloperidol on two-way ac tive avoidance. We assessed the avoidance acquisition of the following drug treatment groups in which all animals received two injections prior to tes ting: vehicle + vehicle, vehicle + haloperidol (0.1 mg/kg, i.p.), clozapine (2.5, 5.0 or 10 mg/kg, i.p.) + haloperidol (0.1 mg/kg, i.p.), or clozapine (2.5, 5.0 or 10 mg/kg, i.p.) + vehicle. Haloperidol-pretreated animals sho wed markedly impaired active avoidance, deficits which were improved by 2.5 and 5 mg/kg but not by 10 mg/kg clozapine pretreatment. These data suggest that the disruptive effects of haloperidol on conditioned active avoidance partially mirror its capacity to induce catalepsy and extrapyramidal motor symptoms. Furthermore, this study indicates that clozapine may be effectiv e in reducing motor side-effects caused by typical neuroleptics. (C) 2000 L ippincott Williams & Wilkins.