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

The effects of norepinephrine (NE) on the electrophysiological activities o f single hypothalamic arcuate neurons were studied using extracellular reco rding 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 r espond; (2) substitution of low Ca2+-high Mg2+ artificial cerebrospinal flu id (ACSF) for normal ACSF abolished the NE-induced inhibitory effect but fa iled to abolish the excitatory effect; (3) both the NE-induced excitatory a nd inhibitory effects were antagonized partly by phentolamine, prazosin, an d propranolol but not by yohimbine; (4) naloxone and glibenclamide, a block er of adenosine triphosphate-sensitive (K-ATP) channels, blocked the NE-ind uced inhibitory effect; and (5) neurons that were inhibited by NE were also inhibited by morphine and cromakalim, an agonist of K-ATP channels, and mo reover, the morphine-induced inhibitory effect could be blocked by glibencl amide, while the cromakalim-induced inhibitory effect was not blocked by na loxone. These results imply that: (a) NE excites arcuate neurons through a mechanism that is insensitive to lowering the extracellular Ca2+ suggesting a direct postsynaptic response through alpha(1)- and beta-adrenergic recep tors, while NE inhibits cells through at least an inhibitory interneuron in arcuate and so is dependent on a Ca2+-sensitive presynaptic release mechan ism; and (b) the inhibitory interneuron may be opioidergic, being excited f irst through alpha(1)- and beta-adrenergic receptors, after which the relea sed opioids inhibit the neurons being recorded with an involvement of activ ation of K-ATP channels. This possibility needs to be substantiated in much more detail. (C) 2000 Elsevier Science B.V. All rights reserved.