GABA A and GABA B receptors modulating basal and footshock-induced nitric oxide releases in rat prefrontal cortex

Abstract

Using an in vivo brain microdialysis technique, we measured extracellular levels of nitric oxide (NO) metabolites (NO x −) in the medial prefrontal cortex (mPFC) upon perfusion of γ-aminobutyric acid (GABA) receptor antagonists as well as agonists, and also examined the effects of GABA receptor agonists on mild intermittent footshock-induced NO releases in the mPFC in conscious rats. Perfusion of either bicuculline methiodide, a GABA A receptor antagonist, or saclofen, a GABA B receptor antagonist, through a microdialysis probe resulted in dose-dependent increases in NO x − levels. Higher-dose perfusion of either muscimol (50 μM), a GABA A receptor agonist, or baclofen (250 μM), a GABA B receptor agonist resulted in a significant decrease in NO x − levels. The elevated levels of NO x − after mild intermittent footshock were attenuated by perfusion of either muscimol (10 μM) or baclofen (50 μM), either of which alone did not affect basal NO x − levels. These findings are likely to provide helpful clues to our understanding of the inhibitory modulation of basal and footshock-induced NO metabolites releases by GABA A and GABA B receptors in the mPFC.