Chronic treatment with clozapine, but not haloperidol, increases striatal ecto-5'-nucleotidase activity in rats

In the search for differential mechanisms underlying clozapine's superior antipsychotic efficacy, the purinergic system has been considered, since an antagonist of the adenosine receptor A(2A) was shown to block clozapine acute effects on c-fos expression in rat striatum. Further investigating the interaction of clozapine with the purinergic system, we studied the effects of chronic treatment (28 days, intraperitoneal) with clozapine (25 mg/kg) and haloperidol (1.5 mg/kg) on the activity of ectonucleotidases in the striatum and hippocampus of rats. Clozapine selectively increased striatal 5'-nucleotidase activity (22%) compared to control and haloperidol groups. In vitro, neither drug affected enzyme activities. These results reinforce the differential effects of clozapine compared to haloperidol on the purinergic system.