TONIC GABAERGIC MODULATION OF STRIATAL DOPAMINE RELEASE STUDIED BY IN-VIVO MICRODIALYSIS IN THE FREELY MOVING RAT

GABA(A) and GABA(B) receptor agonists and antagonists were administered locally in the striatum of intact and kainic acid lesioned rats. (+/-)-Baclofen, a GABA(B) receptor agonist, significantly decreased the level of extracellular dopamine in the striatum of intact rats. (+/-)-Phaclofen, a GABA(B) receptor antagonist, increased the level of extracellular dopamine in the striatum of intact rats and to a lesser extent in the striatum after kainic acid lesion. Pregnanolone (5 beta-pregnan-3 alpha-ol-20-one), a positive allosteric modulator of the GABA, receptor, significantly decreased the level of extracellular dopamine in intact rats. (-)-Bicuculline, a GABA(A) receptor antagonist, increased the level of extracellular dopamine in the striatum of intact rats, but failed to increase the level of extracellular dopamine after kainic acid lesion. The release of extracellular dopamine, due to infusion of phaclofen or bicuculline, was totally suppressed by tetrodotoxin. These results support a direct influence of GABA on the dopaminergic terminals via presynaptic GABA(B) receptors, while the effects via the GABA(A) receptor seem to be postsynaptic and mediated by striatal interneurons or the striatonigral feedback loop.