SUPERSENSITIVITY OF DOPAMINE RECEPTORS, INDUCED BY NEUROLEPTICS

Different neuroleptics caused dopamine receptor blockade (antagonism against methylphenidate-induced compulsive gnawing) for varying lengths of time [in mice]. When the receptor blockade had expired, supersensitivity to dopamine agonists (occurrence of apomorphine-induced compulsive gnawing and enhancement of methylphenidate-induced gnawing) developed and persisted for varying periods of time. The degree and duration of supersensitivity was related to the degree and duration of the preceding receptor blockade. Inhibition of catecholamine or 5-HT [5-hydroxytryptamine] synthesis had no influence on development of supersensitivity. Stimulation with a dopamine agonist, apomorphine, during the period of the development of supersensitivity did not modify the enhanced receptor supersensitivity. A cholinergic-dopaminergic balance was involved in the manifestation of compulsive behavior during the supersensitivity phase. Tolerance to the dopamine antagonistic effect of a neuroleptic also developed after a single neuroleptic treatment, most likely due to increased sensitivity of the receptors for the dopamine agonist. The dopamine receptor blockade induced by a single dose of a neuroleptic agent is a dynamic phenomenon which in the course of time is replaced by an increased sensitivity of the receptors to dopamine agonists. Noradrenergic or 5-HT neuron systems do not seem to be involved in the neuroleptic-induced supersensitivity, whereas a dopaminergic-cholinergic balance is operative in the supersensitivity situation.