GABAA and GABAB receptors differentially regulate striatal acetylcholine release in vivo

Microdialysis was used to study the effects of selective GABAergic agents on striatal acetylcholine (ACh) release in awake, freely moving rats. Local perfusion with the GABA_A agonist muscimol dramatically reduced striatal ACh release, while the GABA_B agonist baclofen caused only minor decreases in ACh release. Co-perfusion with the GABA_A antagonist bicuculline diminished the muscimol-induced decrease in ACh release. Likewise, co-perfusion with the GABA_B antagonist 2-hydroxysaclofen attenuated the baclofen-induced reduction in ACh release. Bicuculline alone markedly increased striatal ACh release, but 2-hydroxysaclofen by itself had no effect. These results suggest that GABA tonically regulates striatal ACh release primarily through stimulation of inhibitory GABA_A receptors.