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 3776, 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-HT_1A 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-HT_1A 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.