Morphine and naltrexone modulate D 2 but not D 1 receptor induced motor behavior in MPTP-lesioned monkeys

Morphine and naltrexone modulate D 2 but not D 1 receptor induced motor behavior in MPTP-lesioned... 213 118 118 4 4 R. J. Vermeulen B. Drukarch E. C. Wolters J. C. Stoof A. N. M. Schoffelmeer M. C. Rob Sahadat C. Goosen Department of Neurology, Medical Faculty Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit Van der Boechorststraat 7 NL-1081 BT Amsterdam The Netherlands Department of Pharmacology, Medical Faculty Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit Van der Boechorststraat 7 NL-1081 BT Amsterdam The Netherlands TNO Medical Biological Laboratory NL-Rijswijk The Netherlands 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 D 1 and D 2 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 D 2 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 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 μ -receptor antagonist naltrexone was mimicked by the selective δ -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 possible underlying mechanisms and clinical relevance of these findings are discussed. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Morphine and naltrexone modulate D 2 but not D 1 receptor induced motor behavior in MPTP-lesioned monkeys

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Publisher
Springer Journals
Copyright
Copyright © 1995 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
DOI
10.1007/BF02245946
Publisher site
See Article on Publisher Site

Abstract

213 118 118 4 4 R. J. Vermeulen B. Drukarch E. C. Wolters J. C. Stoof A. N. M. Schoffelmeer M. C. Rob Sahadat C. Goosen Department of Neurology, Medical Faculty Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit Van der Boechorststraat 7 NL-1081 BT Amsterdam The Netherlands Department of Pharmacology, Medical Faculty Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit Van der Boechorststraat 7 NL-1081 BT Amsterdam The Netherlands TNO Medical Biological Laboratory NL-Rijswijk The Netherlands 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 D 1 and D 2 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 D 2 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 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 μ -receptor antagonist naltrexone was mimicked by the selective δ -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 possible underlying mechanisms and clinical relevance of these findings are discussed.

Journal

PsychopharmacologySpringer Journals

Published: Apr 1, 1995

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