EFFECT OF SCOPOLAMINE ON THE EFFLUX OF DOPAMINE AND ITS METABOLITES AFTER CLOZAPINE, HALOPERIDOL OR THIORIDAZINE

The extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in th e striatum and the nucleus accumbens were measured in awake, freely-mo ving rats. Clozapine (20 mg/kg, i.p.) increased extracellular DA and H VA in both regions but increased DOPAC only in the striatum. Scopolami ne (1 mg/kg), although it had no effect by itself in the striatum or n ucleus accumbens, inhibited the ability of clozapine to increase extra cellular DA, DOPAC and HVA concentrations in the striatum. The clozapi ne-induced increase in DA in the frontal cortex was not blocked by sco polamine. Haloperidol (1 mg/kg, i.p.) and thioridazine (10 mg/kg, i.p. ) also increased extracellular DA, DOPAC and HVA in the striatum, but scopolamine pretreatment did not inhibit these increases. The results suggest that clozapine differs from haloperidol and thioridazine in th at the effect of clozapine, but not that of the two neuroleptic drugs, to increase DA release in the striatum acutely depends on muscarinic receptor stimulation. These results suggest that clozapine, despite it s strong muscarinic antagonist properties, does not produce full block ade of muscarinic receptors in vivo in the striatum. The interaction o f clozapine with the cholinergic system in the striatum could be relev ant to its lack of ability to produce extrapyramidal symptoms or tardi ve dyskinesia.