GABA and feeding: reversal of overeating by central GABA-transaminase inhibition

Past literature is reviewed briefly which suggests that variations in brain GABA metabolism may be involved in the control of food intake in rats. Recent experiments from the author's laboratory are summarized in which brain GABA has been elevated in adult female rats by intracisternal injection of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS). Central EOS pretreatment produced dose-dependent anorexia in normal subjects and prevented acute overeating in response to systemic insulin (12 U/kg) or 2-deoxyglucose (750 mg/kg). Similar EOS pretreatment essentially reversed the chronic overeating induced by diet palatability, bilateral medial hypothalamic lesions or genetic predisposition (in Zucker fatty rats). The ubiquity of these anorexic effects in the absence of clear motor debilitation suggests that drugs which elevate brain GABA deserve further investigation for their potential utility in the clinical treatment of overeating.