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 [H-3]Sch-23390 and [H-3]spiperone to D-1 and D-2 dopamine receptors , respectively, and [H-3]8-hydroxy-2-(di-n-propylamino)-tetra ([H-3]80 K-DPAT) to 5-HT1A receptors were measured in various brain regions usi ng quantitative autoradiography. Binding to D-2 dopamine receptors was significantly elevated in the caudate-putamen of rats treated with ha loperidol or RWJ 37796 as compared to controls. However, the magnitude of the increase in D-2 binding was significantly greater in haloperid ol-treated (+38%) compared to RWJ 37796-treated (+21%) rats. Haloperid ol treatment also increased binding (+35%) to D-2 dopamine receptors i n the nucleus accumbens, where RWJ 37796 treatment had a considerably smaller effect(+12). No changes in D-1 dopamine or 5-HT1A receptor bin ding were detected following either antipsychotic treatment in any bra in regions studied. Thus, at comparable doses, the novel antipsychotic RWJ 37796 produces less up-regulation of D-2 dopamine receptor bindin g in the striatum than does the typical antipsychotic haloperidol.