Norepinephrine mediates glucoprivic-induced increase in GABA in the ventromedial hypothalamus of rats

Noradrenergic mechanisms in the hypothalamus may be involved in counterregulatory responses to glucoprivic episodes. After 2-deoxy-D-glucose (2-DG; 1.2 mmol/kg iv), extracellular norepinephrine (NE) concentration in the ventromedial hypothalamus (VMN) increased in a bimodal fashion to 251 +/- 39% (P < 0.001) and 150 +/- 17% (P < 0.001) of baseline during the first 30 min. In the lateral hypothalamus (LHA), NE decreased by 30 min (61 +/- 4%, P < 0.001) and no consistent changes were measured in the paraventricular nucleus (PVN). Because the NE response in the VMN after 2-DG followed the same pattern as GABA, the interaction between NE and GABA was evaluated. In the VMN, GABA had little effect on extracellular NE concentrations but NE increased GABA concentrations 166 +/- 13%, (P < 0.01). In the presence of yohimbine (alpha(2)-adrenoceptor antagonist) the first GABA peak after 2-DG was absent, and the second GABA peak was absent in the presence of timolol (beta-adrenoceptor antagonist). These results support an interaction among noradrenergic and GABAergic systems in the VMN during glucoprivation and that increased NE mediates the increase in extracellular GABA after 2-DG.