Autoradiographic analysis of regional alterations in brain receptors following chronic administration and withdrawal of typical and atypical neuroleptics in rats.
Rats were administered haloperidol, clozapine, raclopride, or no drug for 28 days or 8 months. Following a 3 week withdrawal period, in vitro autoradiography was utilized to examine receptor binding for dopamine D2 ([3H]spiperone and [3H]raclopride), dopamine D 1 ([3H]SCH23390), GABA(A) ([3H]muscimol), benzodiazepine ([3H]RO15-1788), and muscarinic ACh receptors ([3H]QNB). [3H]spiperone was elevated in striatal subregions only in haloperidol-treated rats, with the largest increases seen in the 8 month duration animals. Striatal [3H]raclopride binding was increased after both short- and long-term treatment in both haloperidol and raclopride, but not clozapine-treated animals. Clozapine-treated rats showed significant increases in [3H]SCH23390 in the nucleus accumbens after 28-day administration; otherwise no changes were seen for this ligand in any other groups. Increases in [3H]muscimol binding in the substantia nigra reticulata were seen in haloperidol-treated rats after 8 month treatment. Binding of [3H]QNB and [3H]RO151788 were not significantly different from control for any of the drug-treated groups. These data suggest that persisting alterations in receptor binding are primarily seen in dopamine D2 and GABA receptors after withdrawal from chronic administration of haloperidol but not the atypical neuroleptics, clozapine and raclopride.
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Department of Psychology, School of Medicine, University of California, Los Angeles.
Toga
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Ellison
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D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology* / Q000633:toxicity; D001923:Brain Chemistry / Q000187:drug effects*; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000096:biosynthesis / Q000187:drug effects; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000096:biosynthesis / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis / Q000187:drug effects*; D012457:Salicylamides / Q000008:administration & dosage / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D012457:Salicylamides; D020891:Raclopride; D003024:Clozapine; D006220:Haloperidol