Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment.

Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D3 receptors was not changed in any brain region by any of the drug treatments. [3H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [3H]nemonapride and [3H]spiperone binding to dopamine D2-like receptors in the caudate putamen. In contrast, haloperidol caused a small, significant increase in [3H]raclopride binding in the lateral caudate putamen only. Raclopride also elevated, but to a lesser extent [3H]nemonapride and [3H]spiperone binding in caudate putamen, whereas it did not affect [3H]raclopride binding. Clozapine did not significantly change D2-like striatal binding of [3H]nemonaipride, [3H]spiperone or [3H]raclopride. The differences in radioligand binding suggest that [3H]nemonapride and [3H]spiperone may be binding to additional subsets of dopamine D2-like receptors (including D4-like receptors) that are not recognized by [3H]raclopride, which has high affinity for D2 and D3 receptors only. Quantification of [3H]nemonapride or [3H]spiperone binding in the presence of 300 nM raclopride (to block D2 and D3 receptors) revealed that haloperidol, raclopride and clozapine up-regulated D4-like receptors in the caudate putamen using either radioligand. These results suggest that D4-like receptors may be a common site of action of both typical and atypical antipsychotics.