OPIOID RECEPTOR-COUPLED G-PROTEINS IN RAT LOCUS-COERULEUS MEMBRANES -DECREASE IN ACTIVITY AFTER CHRONIC MORPHINE TREATMENT

The nucleus locus coeruleus is involved in the expression of opiate ph ysical dependence and withdrawal, and has been characterized extensive ly with regard to chronic morphine-induced alterations in biochemical and electrophysiological responses. In the present study, the effects of chronic morphine treatment on opioid receptor-coupled G-protein act ivity was investigated in membranes from rat locus coeruleus. Opioid a gonists stimulated low K-m GTPase activity with pharmacology consisten t with mu receptors. Chronic morphine treatment resulted in decreases in both basal and opioid-stimulated low K-m GTPase activity, with no c hange in the percent stimulation by agonist. The decrease in low K-m G TPase activity appeared to be due to a decrease in the V-max of the en zyme, with no change in the K-m for GTP hydrolysis. These results were confirmed by assays of basal and opioid receptor-stimulated [S-35]GTP gamma S binding in the presence of excess GDP. Thus, chronic morphine treatment apparently decreased inhibitory G-protein activity in the l ocus coeruleus without producing any detectable desensitization. These results suggest a potential adaptation at the receptor/transducer lev el which may contribute to other biochemical changes produced in the l ocus coeruleus by chronic morphine treatment.