Serotonergic component of neuroleptic receptors

Abstract

BINDING studies performed in vitro with ³H-haloperidol^1–3, ³H-spiperone^4–5, ³H-dopamine^1–3,6 and ³H-apomorphine^7,8 showed that the specific neuroleptic binding sites in the striatum are dopaminergic. The frontal cortex, however, was much more labelled by ³H-spiperone than by ³H-haloperidol^9,10. The investigations reported here indicate that the neuroleptic receptor sites in the frontal cortex labelled by ³H-spiperone are predominantly serotonergic and virtually identical to those labelled by ³H-LSD. These conclusions were reached from a study of the relative binding affinities of a series of serotonin or dopamine agonists or antagonists for rat frontal cortex and striatal receptors. Significant correlations were obtained between the binding activities in the rat frontal cortex and in vivo potencies in the pharmacological anti-tryptamine test. Similarly, binding activities in the striatum were significantly correlated with the potencies in the anti-apomorphine test. We therefore suggest that serotonergic, as well as dopaminergic, receptors are involved in the mechanism of action of neuroleptic drugs.