THE SELECTIVE 5-HT2A RECEPTOR ANTAGONIST, MDL-100,907, INCREASES DOPAMINE EFFLUX IN THE PREFRONTAL CORTEX OF THE RAT

Diminished function within the mesocortical dopamine system has been t o hypothesized to contribute directly to the negative and indirectly t o the positive symptoms of schizophrenia. Based on the proposed role o f 5-HT2 receptor blockade in the antipsychotic profile of clozapine an d its preferential augmentation of prefrontal dopamine release, we hav e examined the effects of the selective 5-HT2A receptor antagonist, -1 -[2-(4-fluorophenyl)ethyl]-4-piperidine-methanol (MDL 100,907), on dop amine release in the rat medial prefrontal cortex using in vivo microd ialysis. The results indicate that local 5-HT2A receptors exert a toni c inhibitory influence on dopamine efflux in the medial prefrontal cor tex. These observations are consistent with the hypothesis that 5-HT2A receptor blockade contributes to the unique antipsychotic profile of clozapine and that MDL 100,907 may have antipsychotic activity.