THE EFFECTS OF KAINIC ACID LESIONS ON LOCOMOTOR RESPONSES TO HALOPERIDOL AND CLOZAPINE

Spontaneous and amphetamine-elicited locomotor activity in rats is red uced by most clinically effective antipsychotic drugs. We have recentl y demonstrated that intracerebroventricular infusion of kainic acid (K A), which produces cell loss in the hippocampus and other limbic-corti cal brain regions, increases spontaneous and amphetamine-elicited loco motion. The present study determined if KA lesions alter the suppressi ve effects of the antipsychotic drugs, haloperidol and clozapine, on s pontaneous and amphetamine-elicited locomotor behavior. Young adult ma le rats (70 days of age) received intracerebroventricular infusions of vehicle or KA, which produced hippocampal pyramidal cell loss in each rat and more variable cell loss or gliosis in the amygdala, piriform cortex? and laterodorsal thalamus. Thirty days post-surgery, lesioned and control rats were tested once a week for locomotor responses to dr ug treatments. As observed previously, spontaneous locomotor activity and hyperactivity elicited by amphetamine (1.50 mg/kg SC) were greater in lesioned animals than controls. In addition, the level of spontane ous activity and/or amphetamine-elicited hyperlocomotion observed in l esioned rats after haloperidol treatment (0.13, 0.35, or 1.50 mg/kg SC ) was greater than that found in controls. Locomotor responses to low (6.30 mg/kg) and moderate doses of clozapine (20 mg/kg) were similar i n lesioned and control rats? although lesioned rats were more active t han controls following the administration of a high dose of clozapine (30 mg/kg). These data indicate that the hyperactivity associated with limbic-cortical lesions may be insensitive to reversal by haloperidol , yet uniquely sensitive to suppression by clozapine.