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Vol. 290, Issue 2, 881-892, August 1999

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 Withdrawal1

Stéphanie Caillé, Emilio F. Espejo2, Jean-Philippe Reneric, Martine Cador, George F. Koob3 and Luis Stinus

Laboratoire de Neuropsychobiologie des Désadaptations, Center National de le Recherche Scientifique-Unité Mixte de Recherche 5541, BP31, Université Bordeaux II 146, Bordeaux Cedex, France (S.C., J-P.R., M.C., L.S.)

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 alpha 2-adrenoceptor stimulation. Finally, the nycthemeral locomotor activity during spontaneous morphine withdrawal did not differ between the lesioned and the sham-operated rats.

0022-3565/99/2902-0881$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.