Upregulation of galanin binding sites and GalR1 mRNA levels in the mouse locus coeruleus following chronic morphine treatments and precipitated morphine withdrawal

The neuropeptide galanin and its receptors are expressed in the locus coeru leus (LC), a brain circa associated with drug dependence and withdrawal. Al though galanin peptide mRNA levels do not change during withdrawal, it is n ot known whether galanin receptor levels are regulated following opiate wit hdrawal. This study demonstrates that galanin binding ill the LC is upregul ated by chronic-intermittent morphine administration or by precipitated wit hdrawal, but not by acute morphine treatment, suggesting that increased act ivity in the LC may be able to regulate galanin binding sites. Moreover, th e increase in galanin binding sites seems to be caused by increased transcr iption or stabilization of the galanin receptor 1 (GalR1) gene, because the re is a dramatic increase ii? mRNA levels following withdrawal in the LC. I t is, therefore, possible that the increase in GalR1 could be an adaptive m echanism that leads to regulation of cAMP levels and possibly firing rate o f LC neurons. (C) 2000 American College of Neuropsychopharmacology. Publish ed by Elsevier Science Inc. All rights reserved.