The effect of chronic treatment with a novel aryl-piperazine antipsychotic on monoamine receptors in rat brain.
The effects of chronic treatment of rats with RWJ 37796, a novel aryl-piperazine containing antipsychotic drug, on brain monoamine receptors were studied. Rats were treated daily with RWJ 37796 (1.3 mg/kg), the typical antipsychotic haloperidol (1 mg/kg) or vehicle (control) for 21 days, and were sacrificed 3 days after the last injection. Binding of [3H]Sch-23390 and [3H]spiperone to D1 and D2 dopamine receptors, respectively, and [3H]8-hydroxy-2-(di-n-propylamino)-tetralin ([3H]8OH-DPAT) to 5-HT1A receptors were measured in various brain regions using quantitative autoradiography. Binding to D2 dopamine receptors was significantly elevated in the caudate-putamen of rats treated with haloperidol or RWJ 37796 as compared to controls. However, the magnitude of the increase in D2 binding was significantly greater in haloperidol-treated (+38%) compared to RWJ 37796-treated (+21%) rats. Haloperidol treatment also increased binding (+35%) to D2 dopamine receptors in the nucleus accumbens, where RWJ 37796 treatment had a considerably smaller effect (+12). No changes in D1 dopamine or 5-HT1A receptor binding were detected following either antipsychotic treatment in any brain regions studied. Thus, at comparable doses, the novel antipsychotic RWJ 37796 produces less up-regulation of D2 dopamine receptor binding in the striatum than does the typical antipsychotic haloperidol.
Shapiro
L A
LA
Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106, USA.
Offord
S J
SJ
Ordway
G A
GA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors
D014150:Antipsychotic Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D006220:Haloperidol; C086897:mazapertine succinate; C031349:7-hydroxy-2-N,N-dipropylaminotetralin