title: Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment.
abstract: 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.
authors.affiliation: Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, USA.
authors.forename: F I
authors.initials: FI
authors.lastname: Tarazi
authors.forename: W J
authors.initials: WJ
authors.lastname: Florijn
authors.forename: I
authors.initials: I
authors.lastname: Creese
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; D020891:Raclopride; D003024:Clozapine; D006220:Haloperidol