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

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 mug dopamine. The hyperactivity induced by this dose of dopamine was inhibited by the i.p. injection of both the typical neuroleptic agents, haloperidol, fluphenazine, pimozide and clothiapine (0.05--0.5 mg/kg i.p.), and the atypical neuroleptics clozapine, sulpiride and thioridazine (0.5--20 mg/kg i.p.) although, generally, the doses required ot the latter were in the order of 20--100 times those of the typical agents to produce an equivalent effect. In contrast, cataleptic doses of metoclopramide (10--30 mg/kg i.p.) failed to reduce the dopamine-induced hyperactivity: aceperone and propranolol 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 accumbens septi may be of value in the detection of antipsychotic activity.