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Morphine and naltrexone modulate D2 but not D1 receptor induced motor behavior in MPTP-lesioned monkeys

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Abstract

Interactions at the behavioral level between dopamine (DA) and opioid receptors in the mammalian brain have been amply demonstrated. Considering the pivotal role for DA receptors in the pharmacotherapy of Parkinson's disease (PD), these interactions might be clinically relevant. Therefore, in the present study the effects of the opioid antagonist naltrexone and agonist morphine on D1 and D2 receptor induced stimulation of motor behavior in the unilateral MPTP monkey model (n=5) of PD were investigated. The results show that both naltrexone and morphine [0.1–1.0 mg/kg; intramuscular injection (IM)] inhibited D2 receptor stimulated contralateral rotational behavior and hand use induced by administration of quinpirole (LY 171555; 0.01 mg/kg, IM) in a dose-related way. However, no effects of these opioid drugs were observed on D1 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 preferentialμ-receptor antagonist naltrexone was mimicked by the selectiveδ-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 D2 receptor but not D1 receptor controlled motor behavior. The possible underlying mechanisms and clinical relevance of these findings are discussed.

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Authors and Affiliations

  1. Department of Neurology, Medical Faculty, Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Van der Boechorststraat 7, NL-1081 BT, Amsterdam, The Netherlands

    R. J. Vermeulen, B. Drukarch, E. C. Wolters & J. C. Stoof

  2. Department of Pharmacology, Medical Faculty, Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Van der Boechorststraat 7, NL-1081 BT, Amsterdam, The Netherlands

    A. N. M. Schoffelmeer

  3. TNO Medical Biological Laboratory, NL-Rijswijk, The Netherlands

    R. J. Vermeulen, M. C. Rob Sahadat & C. Goosen

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  1. R. J. Vermeulen
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  2. B. Drukarch
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  3. E. C. Wolters
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  4. J. C. Stoof
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  6. M. C. Rob Sahadat
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Vermeulen, R.J., Drukarch, B., Wolters, E.C. et al. Morphine and naltrexone modulate D2 but not D1 receptor induced motor behavior in MPTP-lesioned monkeys. Psychopharmacology 118, 451–459 (1995). https://doi.org/10.1007/BF02245946

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  • DOI: https://doi.org/10.1007/BF02245946

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