The effects of acute and chronic morphine administration on GABA receptor binding

Abstract

The effect of acut and chronic morphine administration and naloxone-precipitated withdrawal on the binding of [ 3H] GABA to its receptor sites in rat brain membranes was investigated. Acut morphine (25 mg/kg) administration produced a decrease in the GABA binding in cerebellum, cortex and striatum. This decrease appears to be due to a selectivel decrease in the number of high-affinity GABA receptor binding sites. In contrast, rats chronically treated with morphine by pellet implantation did not exhibit any changes in GABA receptor binding, except for an increase in pons medulla. However, in rats which were physically dependent, as indicated by naloxone-precipitated withdrawal, GABA binding was decreased significantly in cerebellum and stritum, relative to chronic morphine treatment or placebo pellet controls. This decrease was due to a decrease in the number of low affinity GABA receptor binding sites. Both chronic morphine and naloxone-precipitated withdrawal treatments produced an increase in GABA binding in the pond medulla. These results suggest that morphine may produce some of its effects by modulating GABAergic systems and that high and low affinity GABA receptor sites may paly a differential role during various morphine treatments.