The activity of neurons in the ventromedial hypothalamus (VMH) important for initiating compensatory responses to hypoglycemia is influenced by ambient glucose concentration. In the present study, we used in vivo microdialysis to evaluate interstitial glucose concentrations in rat VMH under various glycemic conditions. Using the zero-net-flux method, steady-state glucose concentration in the VMH was ϳ20% of blood glucose (ϳ1.4 mmol/l) in fed rats but ϳ14% of blood glucose (ϳ0.7 mmol/l) in overnight-fasted rats. During moderate hypoglycemia VMH glucose declined in parallel with blood glucose; however, VMH glucose decreased to a greater degree than blood glucose during a more severe hypoglycemic episode, falling to 10 ؎ 1.2% of blood levels (P < 0.01). To determine whether VMH glucose concentrations were influenced by recurrent episodes of hypoglycemia a second zero-net-flux study was conducted. Steady-state glucose concentrations in the VMH were ϳ20% lower after three episodes of recurrent hypoglycemia, a value 17.8 ؎ 0.8% of blood glucose, although the relative change in VMH glucose levels during the first and fourth hypoglycemic episodes were similar. From these results, we conclude that interstitial glucose concentrations in the VMH are not maintained at a constant level and are more dynamic than previously proposed.

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Chronic pain induces brainstem noradrenergic activation that enhances descending facilitation from the DRt. This suggests that antidepressants inhibiting noradrenaline reuptake may enhance pain facilitation from the brain, counteracting their analgesic effects at the spinal cord.

During insulin-induced hypoglycemia, there is an increase in extracellular norepinephrine (NE) in the ventromedial hypothalamus (VMH). This brain area is known to play an important role in integrated hormonal and behavioral responses to systemic hypoglycemia. Selective glucoprivation restricted to the VMH is both necessary and sufficient to initiate secretion of counterregulatory hormones. The present study was designed to investigate whether increased release of NE in the VMH depends on detection of glucoprivation localized in this area. In awake, chronically catheterized male Sprague-Dawley rats, extracellular NE in the VMH was monitored using 1-mm microdialysis probes perfused with Krebs Ringer buffer (KRB) or KRB + 100 mM d-glucose (d-Glc). During insulin-induced hypoglycemia (glycemic nadir approximately 2.4 mM) extracellular NE was increased to >160% of baseline (P < 0.01) only in the KRB + insulin group. There was no increase in NE from baseline when glucose was added to the perfusate to maintain euglycemia at the periprobe environment. The sympathoadrenal response to hypoglycemia, present in the KRB + insulin group, was attenuated in the d-Glc + insulin group. The present results confirm that noradrenergic activation in the VMH during systemic hypoglycemia depends on detection of glucoprivation locally in this area. These data provide additional support for the importance of increased noradrenergic activity in the VMH in the counterregulatory hormonal responses to hypoglycemia.