Tardive dyskinesia, dopamine receptors, and neuroleptic damage to cell membranes.

The long-term treatment of schizophrenic patients with neuroleptics is associated with neuroleptic accumulation in neuromelanin-containing cells with ensuing nigral cell damage. Thus, in addition to early or short-term up-regulation of D2 dopamine receptors, the late stage denervation supersensitivity may result in a further proliferation of D2 dopamine receptors in those parts of the human striatum controlling mouth-lips-tongue motion. Young individuals, upon reduction or removal of the neuroleptic, may have neural sprouting with subsequent D2 down-regulation and reversal of their dyskinesia. Older individuals may not readily exhibit sprouting and D2 down-regulation, possibly accounting for a more persistent form of dyskinesia.