MORPHINE AND NALTREXONE MODULATE D-2 BUT NOT D-1 RECEPTOR-INDUCED MOTOR BEHAVIOR IN MPTP-LESIONED MONKEYS

Interactions at the behavioral level between dopamine (DA) and opioid receptors in the mammalian brain have been amply demonstrated. Conside ring the pivotal role for DA receptors in the pharmacotherapy of Parki nson's disease (PD), these interactions might be clinically relevant. Therefore, in the present study the effects of the opioid antagonist n altrexone and agonist morphine on D-1 and D-2 receptor induced stimula tion of motor behavior in the unilateral MPTP monkey model (n = 5) of PD were investigated. The results show that both naltrexone and morphi ne [0.1-1.0 mg/kg; intramuscular injection (IM)] inhibited D-2 recepto r stimulated contralateral rotational behavior and hand use induced by administration of quinpirole (LY 171555; 0.01 mg/kg, IM) in a dose-re lated way. However, no effects of these opioid drugs were observed on D-1 receptor stimulated contralateral rotational behavior and hand use induced by administration of SKF 81297 (0.3 mg/kg, IM). Interestingly , the action of the alleged preferential mu-receptor antagonist naltre xone was mimicked by the selective delta-opioid antagonist naltrindole (0.5 mg/kg, IM). From this study it is concluded that in a non-human primate model of PD, alteration of opioid tonus leads to modulation of D-2 receptor but not D-1 receptor controlled motor behavior. The poss ible underlying mechanisms and clinical relevance of these findings ar e discussed.