Clozapine: a serotonin antagonist?

Abstract The effect of clozapine on the central serotonergic transmission system was studied by investigation of open-field motility of rats after microinjection of drugs into nucleus accumbens and median raphe nucleus. Previous work has shown that LSD in low doses potentiates apomorphine-induced hypermotility and that this LSD effect is induced by a serotonin agonist action in median raphe nucleus. Clozapine, injected into median raphe nucleus (0.05 μg), suppressed the LSD effect in the same manner as serotonin antagonists did. Since α-adrenergic drugs, injected into median raphe nucleus, caused locomotor stimulant effects, an α-adrenalytic action of clozapine was excluded. Clozapine, injected into nucleus accumbens (0.2 μg), increased apomorphine-induced hypermotility, whereas the dopamine antagonist haloperidol suppressed it. Our results suggest a serotonin antagonist action of clozapine.