γ-aminobutyric acid A (GABA A) receptor modulation of morphine inhibition of norepinephrine release

Abstract

Agents that enhance γ-aminobutyric acid (GABA) neurotransmission can modulate certain effects of opioids, such as analgesia. In this study, the interaction between morphine and GABAergic agents on the release of [ 3H]norepinephrine ([ 3H]NE) from rat frontal cortical slices was examined. GABA (10 −4M), enhanced potassium-stimulated [ 3H]NE release and reversed the inhibitory effect of 10 −6 M morphine. GABA and muscimol modulated the inhibitory effect of morphine in a noncompetitive manner. Bicuculline methiodide (10 −4 M) reduced the effect of GABA in the absence of morphine, and appeared to reduce the effect of GABA in the presence of morphine, although the latter effect was not statistically significant from the controls. While the GABA a agonist muscimol mimicked the effect of GABA, the GABA B agonist baclofen did not affect the release of [ 3H]NE in the absence or the presence of 10 −6M morphine. These results support the involvement of GABA A receptors in modulating the action of opioids on the noradrenergic system in the cerebral cortex of the rat.