PMID: 2498635May 1, 1989Paper

A novel action of morphine in the rat locus coeruleus: persistent decrease in adenylate cyclase

Molecular Pharmacology
D BeitnerE J Nestler

Abstract

This study describes a novel action of morphine on adenylate cyclase activity in the rat locus coeruleus (LC). We have previously shown that acute in vitro morphine inhibits adenylate cyclase activity in isolated LC membranes, whereas chronic in vivo morphine treatment increases enzyme activity in this brain region. We now report that acute in vivo morphine treatment produces a 25-30% decrease in adenylate cyclase activity in the LC, which persists in in vitro assays in the absence of opiates. This in vivo effect is clearly distinct from the acute inhibition of adenylate cyclase observed during exposure of isolated LC membranes to opiates in vitro. The in vivo effect was not reversed by the inclusion of naloxone, an opiate receptor antagonist, in the assay, and acute in vitro opiate inhibition of the enzyme was the same in LC membranes isolated from control and morphine-treated rats. Thus, the in vivo effect does not appear to be due to residual morphine retained in the membrane preparation. This persistent decrease in adenylate cyclase was found to occur in a dose-dependent manner and to be mediated through the actions of morphine at opiate receptors, inasmuch as the inhibition was prevented by concomitant in vivo administrati...Continue Reading

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