Antagonism of the hyperactivity induced by dopamine applied intracerebrally to the nucleus accumbens septi by typical neuroleptics and by clozapine, sulpiride and thioridazine

Abstract

Dopamine administered intracerebrally to the nucleus accumbens septi was shown to induce a dose-dependent hyperactivity following pretreatment with nialamide. This effect was optimum following the injection of 50 μg dopamine. The hyperactivity induced by this dose of dopamine was inhibite by the i.p. injection of both the typical neuroleptic agents, haloperidol, fluphenazine, pimozide and clothiapine (0.5–.5 mg/kg i.p.), and the atypical neuroleptics clozapine, sulpiride and thioridazine (0.5–20 mg/kg i.p.) although, generally, the doses required of the latter were in the order of 20–100 times those of the typical agents to produce and equivalent effect. In contrast, cataleptic doses of metoclopramide (10–30 mg/kg i.p.) failed to reduce the dopamine-induced hyperactivity: aceperone and propanolol were similarly ineffective. However, inhibition of hyperactivity was recorded following the peripheral administration of the antimanic drug, IB503. It is suggested that the ability of a drug to antagonise the hyperactivity induced by the injection of dopamine into the nucleus septi may be of value in the detection of antipsychotic activity.