Norepinephrine modulates single hypothalamic arcuate neurons via alpha(1)and beta adrenergic receptors

Brain Res. 2000 Jun 30;869(1-2):146-57. doi: 10.1016/s0006-8993(00)02380-5.

Abstract

The effects of norepinephrine (NE) on the electrophysiological activities of single hypothalamic arcuate neurons were studied using extracellular recording of 385 neurons from 169 brain slices in rats. The results showed that: (1) of 236 neurons selected randomly and tested with NE application, 137 (58.0%) were excited, 67 (28.4%) were inhibited, and 32 (13.6%) failed to respond; (2) substitution of low Ca(2+)-high Mg(2+) artificial cerebrospinal fluid (ACSF) for normal ACSF abolished the NE-induced inhibitory effect but failed to abolish the excitatory effect; (3) both the NE-induced excitatory and inhibitory effects were antagonized partly by phentolamine, prazosin, and propranolol but not by yohimbine; (4) naloxone and glibenclamide, a blocker of adenosine triphosphate-sensitive (K(ATP)) channels, blocked the NE-induced inhibitory effect; and (5) neurons that were inhibited by NE were also inhibited by morphine and cromakalim, an agonist of K(ATP) channels, and moreover, the morphine-induced inhibitory effect could be blocked by glibenclamide, while the cromakalim-induced inhibitory effect was not blocked by naloxone. These results imply that: (a) NE excites arcuate neurons through a mechanism that is insensitive to lowering the extracellular Ca(2+) suggesting a direct postsynaptic response through alpha(1)- and beta-adrenergic receptors, while NE inhibits cells through at least an inhibitory interneuron in arcuate and so is dependent on a Ca(2+)-sensitive presynaptic release mechanism; and (b) the inhibitory interneuron may be opioidergic, being excited first through alpha(1)- and beta-adrenergic receptors, after which the released opioids inhibit the neurons being recorded with an involvement of activation of K(ATP) channels. This possibility needs to be substantiated in much more detail.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Calcium / deficiency
  • Cromakalim / pharmacology
  • Female
  • Glyburide / pharmacology
  • In Vitro Techniques
  • Locus Coeruleus / cytology
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / metabolism
  • Magnesium / pharmacology
  • Male
  • Morphine / pharmacology
  • Naloxone / pharmacology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Norepinephrine / metabolism*
  • Phentolamine / pharmacology
  • Prazosin / pharmacology
  • Propranolol / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / metabolism*
  • Yohimbine / pharmacology

Substances

  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, beta
  • Cromakalim
  • Yohimbine
  • Naloxone
  • Morphine
  • Propranolol
  • Magnesium
  • Glyburide
  • Calcium
  • Norepinephrine
  • Prazosin
  • Phentolamine