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 D 1 and D 2 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 D 2 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 D 2 binding was significantly greater in haloperidol-treated (+ 38%) compared to RWJ 37796-treated (+ 21%) rats. Haloperidol treatment also increased binding (+ 35%) to D 2 dopamine receptors in the nucleus accumbens, where RWJ 37796 treatment had a considerably smaller effect (+ 12). No changes in D 1 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 D 2 dopamine receptor binding in the striatum than does the typical antipsychotic haloperidol.