SENSITIVITY OF DOPAMINE D-2 RECEPTORS FOLLOWING LONG-TERM TREATMENT WITH ROXINDOLE

The selective presynaptic dopamine D-2 receptor agonist roxindole was studied in specific pre- and postsynaptic models in rats to see whethe r it induced changes in dopamine D-2 receptor sensitivity. Following t reatment with 0.3 or 3 mg/kg per day i.p. for 21 days, the reversal of gamma-butyrolactone-induced striatal dihydroxyphenylalanine accumulat ion was unchanged as compared to that after acute treatment. The effic acy of roxindole in this model was not decreased after long-term treat ment. Likewise, treatment for 19 days with up to 10 mg/kg per day i.p. failed to induce behavioral supersensitivity, i.e. potentiation of ap omorphine-induced stereotypies. In a cotreatment paradigm with haloper idol (1 mg/kg per day p.o.), roxindole (10 mg/kg per day i.p.) did not alter the behavioral supersensitivity measured after a drug washout p hase as compared to the effect of haloperidol alone; however, stereoty pies were observed after termination of haloperidol but continuation o f roxindole treatment. In contrast, roxindole (10 mg/kg i.p.) induced only weak stereotypies in haloperidol-sensitized rats when given after the washout phase instead of apomorphine. The results indicate that r oxindole induces neither desensitization of presynaptic nor supersensi tization of postsynaptic dopamine D-2 receptors. Nevertheless, in add- on clinical studies with neuroleptics, switching of treatment regimens should be performed gradually over several days until further experie nce is available.