Graded increases in brain GABA: differential effects on feeding and other behaviours in rats

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.