The effect of chronic neuroleptic administration on cerebral dopamine receptor function.

Acute administration of neuroleptic drugs causes blockade of cerebral dopamine receptors. It has been discovered that chronic administration of neuroleptic drugs may have different effects on cerebral dopamine systems. Initial antagonism of dopamine mediated behaviour, such as stereotypy, disappears and may be replaced by supersensitivity to dopamine agonists. Changes also occur in biochemical indices of dopamine receptors, such as in the number and affinity of specific binding sites identified by 3H-ligands labelling D-2 receptors, and in dopamine-stimulated adenylate cyclase activity. All these changes occur obviously in the striatum in response to chronic administration of a range of neuroleptic drugs. Lesser changes take place in the mesolimbic dopamine system. What happens in the mesocortical dopamine pathways is unknown. The consequence of such adaptive responses to chronic neuroleptic therapy may be of importance to understanding of tardive dyskinesia and schizophrenia.