GABAergic modulation of serotonin release in the rat subfornical organ area

The present study was carried out to examine whether gamma-aminobutyric acid (GABA) receptor mechanisms are involved in the release of serotonin (5-hydroxytryptamine, 5-HT) in the subfornical organ (SFO) using intracerebral microdialysis techniques. Perfusion with the GABA receptor antagonists as well as agonists was performed in the region of the SFO through a microdialysis probe and extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in freely moving rats. Perfusion with the GABA(A) receptor antagonist bicuculline (10 and 50 mu M), but not the GABA(B) receptor antagonist phaclofen (10 and 50 mu M), increased dialysate 5-HT and 5-HIAA concentrations in the SFO area, suggesting that the GAB(A)ergic system may tonically inhibit the 5-HT release in the SFO area through GABA(A) receptors. Higher perfusion with the GABA(A) receptor agonist muscimol (50 mu M) or the GABA(B) receptor agonist baclofen (250 mu M) decreased extracellular levels of 5-HT and 5-HIAA in the SFO area. Nonhypotensive hypovolemia induced by subcutaneous injection of polyethylene glycol (PEG, 30%, 5 ml) significantly enhanced the 5-HT and 5-HIAA concentrations in the SFO area. The enhanced 5-HT and 5-HIAA levels elicited the PEG treatment were reduced by perfusion with muscimol (10 M), but not by baclofen (50 mu M). These results show the involvement of both GABA(A) and GABA(B) receptors in the modulation of the 5-HT release in the SFO area, and imply that the GABA(A) receptor mechanism may be importance for the serotonergic regulatory system of body fluid balance. (C) 2016 Elsevier Ireland Ltd. All rights reserved.