In vivo alteration in hypothalamic amino acid synthesis during perfusion of ethanol and morphine in unrestrained rat

In the freely moving rat U-¹⁴C]glucose was microinjected through a guide tube to label a discrete site in the hypothalamus. After 10 min, a push-pull cannula was used to perfuse an artificial CSF within the site at a rate of 25 l/min. During the fourth 5 min perfusion of each series, one of three concentrations of either ethanol (94–471 mM) or morphine SO₄ (0.13–1.3 mM) was added to the perfusate. Each sample of perfusate was assayed for its content of GABA, glutamate, alanine, aspartate, glycine and glutamine by two-dimensional, thin-layer chromatography. The results show that within a circumscribed region of the dorsal hypothalamus, the synthesis of ¹⁴C]glycine and ¹⁴C]glutamine was enhanced by ethanol and morphine, respectively. Ethanol generally augmented also the synthesis of GABA, glutamate, and glutamine at sites reactive to the compound. Within the same sites, morphine increased the synthesis of glycine. Other amino acids were not significantly different from the control. Thus, anatomically specific and selective changes in amino acid activity are produced within the rat's hypothalamus in response to the localized presence of ethanol or morphine suggesting the involvement of certain amino acids in the action of these addictive compounds within the hypothalamus.