Elevations of brain
gamma-aminobutyric acid (
GABA) induced by inhibitors of
GABA transaminase (
GABA-T) are known to induce a number of functional effects including depression of food intake. The aim of the present study was to determine the brain
GABA elevation threshold for changes in feeding and several other behaviours, in an effort to clarify whether feeding changes might be secondary to other functional deficits. To this end, various doses of the
GABA-T inhibitors
ethanolamine-o-sulfate (EOS) and
gamma-vinyl GABA (GVG) were injected intracisternally and effects on whole brain
GABA, food and water intake, open field activity,
catalepsy indices,
pain sensitivity, and core temperature were assessed 24 h later. Progressive increases in brain
GABA levels were found to differentially affect the responses studied. At the low end of the continuum, significant decreases in feeding behaviour were associated with relatively modest increases in brain
GABA (40-60%). At higher levels of
GABA elevation (greater than 100%), changes in motoric functions and rectal temperature became apparent. At still higher levels (greater than 200% increases in brain
GABA), significant antinociceptive effects were detected. These results support the notion that feeding decreases induced by low doses of
GABA-T inhibitors may reflect a fairly specific effect on appetite mechanisms, but also indicate that with increasingly higher doses several other deficits are likely to contribute to the overall decrease in food intake.