GABA and hypothalamic feeding systems

Abstract

Intrahypothalamic injections of the GABA agonist, muscimol (50 ng/μl) in volumes of 0.1 to 0.5 μl were made and the effects on feeding observed. The results of a topographical analysis of the hypothalamus indicated that both the PVH and VMH may be separate, though not necessarily independent, foci of a medial, GABA sensitivity satiety system. Microinjections of muscimol into these areas resulted in feeding which was dose-dependent and was attenuated by pretreatment with the GABA antagonist, bicuculline methiodide. Similar injections of other compounds into the PVH provided further evidence for the involvement of GABA in hypothalamic feeding mechanisms. During the light phase of the lighting cycle 0.3 μl injections of muscimol (100 ng) and flurazepam diHCl (20 μg) increased feeding. Similar injections of glycine (500 ng) did not influence feeding during the light phase. During the dark phase, 0.3 μl injections of bicuculline methiodide (30 ng) or picrotoxin (160 ng) suppressed feeding. Similar injections of carbachol (250 ng) increased drinking during the dark phase. Injections of strychnine (950 ng) during this phase were without effect. Suppression of feeding was observed after muscimol injections into the region lateral to the fornix suggesting that the excitatory lateral hypothalamic feeding system also may have GABAergic components. Injections into this area of compounds (allylglycine or EOS, respectively) that inhibit the GABA synthetic or degradative enzymes also influenced feeding. Injections of allyglycine abolished amphetamine, but not fenfluramine anorexia suggesting that GABAergic and catecholaminergic systems may be interrelated in hypothalamic feeding control.