The nucleus locus coeruleus is involved in the expression of opiate physical dependence and withdrawal, and has been characterized extensively 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 activity was investigated in membranes from rat locus coeruleus. Opioid agonists stimulated low K m GTPase activity with pharmacology consistent with mu receptors. Chronic morphine treatment resulted in decreases in both basal and opioid-stimulated low K m GTPase activity, with no change in the percent stimulation by agonist. The decrease in low K m GTPase activity appeared to be due to a decrease in the V max of the enzyme, with no change in the K m for GTP hydrolysis. These results were confirmed by assays of basal and opioid receptor-stimulated ( 35 S)GTP γ S binding in the presence of excess GDP. Thus, chronic morphine treatment apparently decreased inhibitory G-protein activity in the locus coeruleus without producing any detectable desensitization. These results suggest a potential adaptation at the receptor/transducer level which may contribute to other biochemical changes produced in the locus coeruleus by chronic morphine treatment.
Brain Research – Elsevier
Published: Jan 23, 1997
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