Long-term adaptive changes in striatal dopamine function in response to chronic neuroleptic intake in rats.

Chronic neuroleptic drug administration to rats reverses initial dopamine receptor blockade so that animals exhibit striatal dopamine receptor supersensitivity. This effect may be of functional significance in the whole animal for it is accompanied by increased striatal acetylcholine content and by reversal of the acute increase in striatal acetylcholine release. Continuous drug intake may increase the number of striatal 3H-spiperone binding sites while decreasing the number of 3H-N, n-propylnorapomorphine binding sites. While D-2 adenylate cyclase independent dopamine receptor binding sites increase in number, no change occurs in the number of D-1 sites labelled by 3H-piflutixol despite increased adenylate cyclase activity. Haloperidol and sulpiride differentially alter striatal 3H-acetylcholine and 3H-glutamate release in a manner suggesting selective changes in dopamine receptors lying on striatal cell bodies and on the terminals of corticostriate glutamate terminals. In summary, neuroleptic drugs induce a series of adaptive changes on chronic administration consistent with the development of functional striatal dopamine receptor supersensitivity.