GABAERGIC MODULATION OF STRIATAL CHOLINERGIC INTERNEURONS - AN IN-VIVO MICRODIALYSIS STUDY

Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABA(A) and the GABA(B) receptor. Using in vivo microdialysis, we have studied the effect of intrastriatal application of the GABA(A)-selective compounds muscimol and bicuculline and the GABA(B)-selective compounds baclofen and 2-hydroxysaclofen, agonists and antagonists, respectively, at GABA receptors, on the output of striatal acetylcholine (ACh). Intrastriatal infusion of 1 and 10 mu mol/L concentrations of the GABA(A) antagonist bicuculline resulted in a significant increase in striatal ACh output, whereas infusion of 1 and 10 mu mol/L concentrations of the GABA(A) agonist muscimol significantly decreased the output of striatal ACh. Both compounds were ineffective in changing the output of striatal ACh at lower concentrations. Infusion of concentrations up to 100 mu mol/L of the GABA(B)-selective antagonist 2-hydroxy-saclofen failed to affect striatal ACh output, whereas infusion of 10 and 100 mu mol/L baclofen, but not 0.1 and 1 mu mol/L baclofen, significantly decreased the output of striatal ACh. Thus, agonist-stimulation of GABA(A) and GABA(B) receptors decreases the output of striatal ACh in a dose-dependent fashion, whereas the GABAergic system appears to inhibit tonically the output of striatal ACh via GABA(A) receptors, but not via GABA(B) receptors. We hypothesize that although GABA(A) mediated regulation of striatal ACh occurs via GABA receptors on the cholinergic neuron, the GABA(B) mediated effects may be explained by presynaptic inhibition of the glutamatergic input of the striatal cholinergic neuron