Ibotenic acid lesions reduce noradrenergic activation in ventromedial hypothalamus during hypoglycemia.
Noradrenergic and GABAergic systems in the ventromedial hypothalamus (VMH) are activated during hypoglycemia and initiate part of the compensatory counterregulatory response. Norepinephrine (NE) terminals innervating the VMH originate in glucosensing hindbrain areas, but whether NE activity in the VMH is under local control or in the hindbrain is unclear. To elucidate the role of neurons intrinsic to the VMH on NE release in the VMH during hypoglycemia, ibotenic acid (IBO), an NMDA receptor agonist that selectively destroys cell bodies, was used. In a 2 x 2 factorial study, IBO (3-5 microg/0.5 microL) or vehicle was stereotaxically administered into the VMH of male Sprague-Dawley rats. One week later, NE concentration in the VMH was measured by microdialysis during insulin-induced hypoglycemia (2.0 U/kg) or euglycemia (saline control). Baseline levels of NE were not statistically different (p=0.10) in IBO-treated compared with vehicle-treated rats (13.3+/-2.8 nM vs. 7.9+/-1.1 nM). The initial increase in interstitial NE concentration during hypoglycemia in control rats was absent in IBO-treated rats (p<0.01). In IBO-treated hypoglycemic rats, NE concentrations increased after 45 min to a similar level observed in control rats during the first 20 min of hypoglycemia. These results are consistent with the suggestion that local neurons in the VMH respond to hypoglycemia and modify NE activation in the VMH during hypoglycemia.
Fugo
Kelly R
KR
Neuroscience Program, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.
Lawson
Marc A
MA
Lee Beverly
J
J
D000818:Animals; D017776:Autonomic Pathways / Q000378:metabolism*; D003714:Denervation; D015536:Down-Regulation / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007051:Ibotenic Acid / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D007328:Insulin; D009498:Neurotoxins; D007051:Ibotenic Acid; D009638:Norepinephrine