Possible Interaction: Gamma-Aminobutyric Acid and Morphine

“Both chronic morphine and naloxone-precipitated withdrawal treatments produced an increase in GABA binding in the pons medulla.”

“Both compounds, γ-acetylenic GABA and γ-vinyl GABA, produced an intensification of morphine analgesia, although large doses of γ-acetylenic GABA produced stimulant effects that masked a possible synergism.”

“The results may indicate a relationship between some acute and chronic effects of morphine and GABA concentration in the nervous tissue.”

“Acute administration of morphine induced significant increases of gamma-amino-butyric acid (GABA) content and L-glutamate decarboxylase (GAD) activity at the dorsal parts of the dorsal horn and surroundings of the central canal in the rat spinal cord, in which GABA inhibitory interneurons may play significant roles.”

“In the thalamus, morphine also induced significant increases of GABA content and GAD activity in the vicinity of the ventrolateral part of the ventral nucleus (VM), entopeduncular nucleus (EP), nucleus reuniens thalami (RE), nucleus parafascicularis thalami (PF) and interpeduncular nucleus (IP), respectively.”

“The present results suggest that morphine analgesia may involve mechanisms intensifying the inputs of GABA inhibitory neurons at the levels of the spinal cord and thalamus, where the primary and secondary neurons involved in the perception of pain are terminated respectively.”

“The injection of various doses of morphine , subcutaneously, or of beta-endorphin, intraventricularly, changes the turnover rate of gamma-aminobutyric acid (TRGABA) in the substantia nigra, globus pallidus and nucleus caudatus.”

“Abstract The findings from our laboratory indicated that pharmacological manipulations of GABA system modified morphine analgesia, tolerance and physical dependence.”

“6 or the administration of GABA agonists, e.g. muscimol and baclofen”~’* enhances morphine analgesia.”

“ Morphine administration increased extracellular serotonin and GABA concentrations significantly within 20min, as shown previously.”

“ Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation.”

“Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels.”

“Therefore, it seems that long-term morphine alters some properties of GABA system so that the responsive rate of GABA(A) receptors not only to its antagonists, but also to its agonists will change differently.”