Amphetamine releases GABA in striatum of the freely moving rat: involvement of calcium and high affinity transporter mechanisms.

Using microdialysis the effect was investigated of amphetamine (AMPH) infusions into the striatum on the release of GABA in the freely moving rat. AMPH (5, 10 and 20 microg/microl), infused through a microdialysis probe at the rate of 2.5 microl/min, produced a dose-related increase in extracellular concentrations of GABA. At the highest dose (20 microg/microl), AMPH increased GABA from 0.08 +/- 0.01 to 0.67 +/- 0.14 microM. Increases in extracellular GABA produced by AMPH were both calcium-dependent and high affinity GABA transporter-mediated. A medium free of calcium reduced the increase of extracellular GABA produced by AMPH by 37%. Nipecotic acid (2, 4 and 8 mM), a specific GABA re-uptake blocker, significantly attenuated increases in extracellular GABA, but not GLU, produced by AMPH (20 microg/microl). This study is the first in vivo evidence showing the release of GABA produced by AMPH through a high affinity transporter mechanism.