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

R J Vermeulen, B Drukarch, M C Sahadat, C Goosen, A N Schoffelmeer, E C Wolters, J C Stoof

Research output: Contribution to journalArticleAcademicpeer-review

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 preferential mu-receptor antagonist naltrexone 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 D2 receptor but not D1 receptor controlled motor behavior. The possible underlying mechanisms and clinical relevance of these findings are discussed.

Original languageEnglish
Pages (from-to)451-9
Number of pages9
JournalPsychopharmacology
Volume118
Issue number4
Publication statusPublished - Apr 1995

Cite this

Vermeulen, R. J., Drukarch, B., Sahadat, M. C., Goosen, C., Schoffelmeer, A. N., Wolters, E. C., & Stoof, J. C. (1995). Morphine and naltrexone modulate D2 but not D1 receptor induced motor behavior in MPTP-lesioned monkeys. Psychopharmacology, 118(4), 451-9.
Vermeulen, R J ; Drukarch, B ; Sahadat, M C ; Goosen, C ; Schoffelmeer, A N ; Wolters, E C ; Stoof, J C. / Morphine and naltrexone modulate D2 but not D1 receptor induced motor behavior in MPTP-lesioned monkeys. In: Psychopharmacology. 1995 ; Vol. 118, No. 4. pp. 451-9.
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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 preferential mu-receptor antagonist naltrexone 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 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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Vermeulen, RJ, Drukarch, B, Sahadat, MC, Goosen, C, Schoffelmeer, AN, Wolters, EC & Stoof, JC 1995, 'Morphine and naltrexone modulate D2 but not D1 receptor induced motor behavior in MPTP-lesioned monkeys' Psychopharmacology, vol. 118, no. 4, pp. 451-9.

Morphine and naltrexone modulate D2 but not D1 receptor induced motor behavior in MPTP-lesioned monkeys. / Vermeulen, R J; Drukarch, B; Sahadat, M C; Goosen, C; Schoffelmeer, A N; Wolters, E C; Stoof, J C.

In: Psychopharmacology, Vol. 118, No. 4, 04.1995, p. 451-9.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Morphine and naltrexone modulate D2 but not D1 receptor induced motor behavior in MPTP-lesioned monkeys

AU - Vermeulen, R J

AU - Drukarch, B

AU - Sahadat, M C

AU - Goosen, C

AU - Schoffelmeer, A N

AU - Wolters, E C

AU - Stoof, J C

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N2 - 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 preferential mu-receptor antagonist naltrexone 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 D2 receptor but not D1 receptor controlled motor behavior. The possible underlying mechanisms and clinical relevance of these findings are discussed.

AB - 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 preferential mu-receptor antagonist naltrexone 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 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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KW - Behavior, Animal

KW - Functional Laterality

KW - Macaca mulatta

KW - Male

KW - Morphine

KW - Naltrexone

KW - Receptors, Dopamine D1

KW - Receptors, Dopamine D2

KW - Receptors, sigma

KW - Journal Article

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SP - 451

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JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

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