Further Studies of the Role of Opioid Receptors in the Nigra in the Morphine Withdrawal Syndrome

Author(s)

Angela M. Waguespack, Nova Southeastern UniversityFollow
A. A. BaumeisterFollow
A. L. Richard
L. Richmond-Landeche
M. J. Hurry

Document Type

Article

Publication Title

Neuropharmacology

ISSN

0028-3908

Publication Date

9-1992

Abstract

Bilateral injection of naloxone (3.0–30.0 nmol) into the substantia nigra of morphine-dependent rats produced a withdrawal syndrome consisting of wet-dog shakes, teeth chattering, irritability to touch, diarrhea and hypothermia. Intense wet-dog shakes and grooming were observed after intranigral injection of the mu selective antagonist d-Phe-Cys-Try-d-Trp-Orn-Thr-Pen-Thr-NH₂ (CTOP, 3.0–30.0 nmol) in morphine-dependent animals. Body temperature after 30.0 nmol CTOP was significantly increased. A significant positive correlation between body temperature and wet-dog shakes was observed in morphine-dependent animals that received CTOP. Intranigral injection of β-funaltrexamine (β-FNA, 10.0 nmol), an irreversible mu antagonist, produced no signs of withdrawal in morphine-dependent animals. However, intranigrat injection of β-FNA (1.0–3.0 nmol) suppressed the antinociceptive effect of the mu-selective agonist, d-Ala²,N-Me-Phe⁴,Gly⁵-ol-enkephalin (DAGO, 1.0 nmol). The withdrawal syndrome produced by CTOP (10.0 nmol) was not suppressed by the administration of U50,488H (10.0 nmol), a kappa agonist, suggesting that the absence of an effect of β-FNA was not due to its kappa agonist activity. Neither the delta-selective antagonist, naltrindole (NTI, 10.0 nmol) nor the kappaselective antagonist, nor-binaltorphimine (nor-BNI, 10.0 nmol) produced withdrawal. Only wet-dog shakes were observed when CTOP, NTI and nor-BNI (5 nmol each) were administered together into the nigra. These studies suggest an involvement of mu receptors in the nigra in the wet-dog shakes and thennoregulatory dysfunction that occur during withdrawal of morphine. However, the subtypes ofopioid receptors in the nigra, that mediate the other signs of morphine withdrawal remain obscure.

DOI

10.1016/0028-3908(92)90119-A

Volume

31

Issue

9

First Page

835

Last Page

841

NSUWorks Citation

Waguespack, A. M., Baumeister, A. A., Richard, A. L., Richmond-Landeche, L., Hurry, M. J. (1992). Further Studies of the Role of Opioid Receptors in the Nigra in the Morphine Withdrawal Syndrome. Neuropharmacology, 31(9), 835-841.
Available at: https://nsuworks.nova.edu/cps_facarticles/501