Glutamate and GABA (γ- amino butyric acid) are amino acids produced locally in the hypothalamus. J Comp Neurol. 1990 Dec 22;302(4):1019-37.   Together they constitute the most abundant neurotransmitters in the hypothalamus. Science. 1990 Nov 30;250(4985):1276-8. Glutamate and GABA can both stimulate feeding in rats.

NMDA (n-methyl d-Aspartic acid) an agonist at the glutamate receptor, when injected into the rat lateral hypothalamus  stimulates short-lived feeding lasting for 10 minutes. Brain Res. 1993 Jun 4;613(1):88-95   This transient feeding stimulation is in contrast to the longer duration of feeding elicited by other neuropeptides as NPY, and hence suggests an orexigenic effect mediated independent of those neuropeptides.

GABA has been shown to inhibit POMC gene expression.  Ann N Y Acad Sci. 1993 May 31;680:260-78.   GABA-ergic fibres have synaptic contacts with β-endorphin containing neurons in the ARC, making it likely that GABA-ergic synapses may regulate the output of POMC-derived peptides. GABA is co-expressed in NPY and Galanin producing neurons in the ARC. Brain Res. 1997 May 9;756(1-2):283-6.   Muscimol, a GABA receptor agonist, also inhibits POMC gene expression, and has a synergistic feeding effect when injected with NPY directly into the PVN. Endocrinology. 1999 Feb;140(2):933-40  A co-release of GABA and NPY in the PVN could thus produce a combined effect  in physiological feeding stimulation.  Muscimol when injected into the hypothalamic nuclei (VMN, DMN, or PVN) stimulates feeding lasting for up to 30 minutes.  Life Sci. 1981 Sep 21;29(12):1213-8.

GABA has traditionally been considered an inhibitory neurotransmitter. J Comp Neurol. 1990 Dec 22;302(4):1019-37.   Hence, rather than functioning as a directly acting facilitatory orexigen, it is possible that GABA may exert an inhibitory effect on an existing anorexigenic tone in the brain, thus indirectly facilitating feeding. This might be mediated by decreasing α-MSH release  Ann N Y Acad Sci. 1993 May 31;680:260-78.  or by rendering crucial target sites highly responsive to NPY.

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