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

It has been suggested that an increase firing rate of noradrenergic neurons of the locus ceruleus is responsible for the opiate withdrawal syndrome. H owever, 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 determ ine the effect of the almost complete 6-hydroxydopamine lesion of noradrene rgic neurons (94%) of the locus ceruleus on various components of the opiat e withdrawal syndrome and on its protection by clonidine. Morphine dependen ce was induced by s.c. implantation of morphine pellets (2 x 75 mg base). T he following paradigms were used: 1) naloxone-induced conditioned place ave rsion, 2) naloxone-precipitated acute opiate withdrawal syndrome, 3) nycthe meral locomotor activity as a measure of spontaneous opiate withdrawal. The results showed that quasi-total lesion of noradrenergic neurons of the loc us ceruleus did not modify opiate dependence as revealed by naloxone-induce d conditioned place aversion and the expression of an acute morphine withdr awal syndrome. Moreover, clonidine prevented the opiate withdrawal syndrome in both lesioned and sham-operated rats, suggesting that the action of clo nidine is certainly mediated through postsynaptic alpha(2)-adrenoceptor sti mulation. Finally, the nycthemeral locomotor activity during spontaneous mo rphine withdrawal did not differ between the lesioned and the sham-operated rats.