Abstract
It has been suggested that an increase firing rate of noradrenergic neurons of the locus ceruleus is responsible for the opiate withdrawal syndrome. However, lesion studies have indicated that the noradrenergic neurons of the locus ceruleus are not essential for either the expression or suppression by clonidine of opiate withdrawal. The present study was designed to determine the effect of the almost complete 6-hydroxydopamine lesion of noradrenergic neurons (94%) of the locus ceruleus on various components of the opiate withdrawal syndrome and on its protection by clonidine. Morphine dependence was induced by s.c. implantation of morphine pellets (2 × 75 mg base). The following paradigms were used: 1) naloxone-induced conditioned place aversion, 2) naloxone-precipitated acute opiate withdrawal syndrome, 3) nycthemeral locomotor activity as a measure of spontaneous opiate withdrawal. The results showed that quasi-total lesion of noradrenergic neurons of the locus ceruleus did not modify opiate dependence as revealed by naloxone-induced conditioned place aversion and the expression of an acute morphine withdrawal syndrome. Moreover, clonidine prevented the opiate withdrawal syndrome in both lesioned and sham-operated rats, suggesting that the action of clonidine is certainly mediated through postsynaptic α2-adrenoceptor stimulation. Finally, the nycthemeral locomotor activity during spontaneous morphine withdrawal did not differ between the lesioned and the sham-operated rats.
Footnotes
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Send reprint requests to: Dr. Luis Stinus, Laboratory de Neuropsychobiologie des Désadaptations, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 5541, BP31, Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. E-mail:luis.stinus{at}lnpb.u-bordeaux2.fr
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↵1 This work was supported by grants from the University of Bordeaux 2, the Center National de le Recherche Scientifique, the Conseil Regional d’Aquitaine, the Ministère de l’Enseignement Supérieur et de la Recherche and the Fondation pour la Recherche Médicale. This is publication number 12130-NP from The Scripps Research Institute. G.F.K. was supported in part by research Grant DA 04043 from the National Institute on Drug Abuse. This work was carried out in accordance with the Declaration of Helsinki, the Guide and Use of Laboratory Animals as adopted and promulgated by the United States National Institutes of Health, the European Communities Council Directives (86/609/EEC, 24 November 1986), and the French Directives concerning the Use of Laboratory Animals (Decret 87–848, 19 October 1987).
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↵2 Present address: Depto de Fisiologia Médica y Biofisica, Universidad de Sevilla, E-41009 Sevilla, Spain.
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↵3 Present address: Department of Neuropharmacology, CNV-7, The Scripps Research Institute, La Jolla, CA 92037.
- Abbreviations:
- NA
- noradrenaline
- LC
- locus coeruleus
- NA-LC neurons
- noradrenergic neurons from locus coeruleus
- 6-OHDA
- 6-hydroxydopamine neurotoxin
- G-H score
- Gellert and Holtzman score
- Received February 9, 1999.
- Accepted April 14, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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In this issue
Total Neurochemical Lesion of Noradrenergic Neurons of the Locus Ceruleus Does Not Alter Either Naloxone-Precipitated or Spontaneous Opiate Withdrawal nor Does It Influence Ability of Clonidine To Reverse Opiate Withdrawal
