Elevated endogenous GABA concentration attenuates glutamate-glutamine cycling between neurons and astroglia.

In this study, the relationship between endogenous brain GABA concentration and glutamate-glutamine cycling flux (V (cyc)) was investigated using in vivo (1)H and (1)H{(13)C} magnetic resonance spectroscopy techniques. Graded elevations of brain GABA levels were induced in rat brain after administration of the highly specific GABA-transaminase inhibitor vigabatrin (gamma-vinyl-GABA). The glial-specific substrate [2-(13)C]acetate and (1)H{(13)C} magnetic resonance spectroscopy were used to measure V (cyc) at different GABA levels. Significantly reduced V (cyc) was found in rats pretreated with vigabatrin. The reduction in group mean V (cyc) over the range of GABA concentrations investigated in this study (1.0 +/- 0.3-5.1 +/- 0.5 micromol/g) was found to be nonlinear: Delta V (cyc)/V (cyc) = [GABA (micromol/g)](-0.35 )- 1.0 (r (2) = 0.98). The results demonstrate that V (cyc) is modulated by endogenous GABA levels, and that glutamatergic and GABAergic interactions can be studied in vivo using noninvasive magnetic resonance spectroscopy techniques.