title: Norepinephrine inhibits neurons of the intermediate subnucleus of the lateral septum via alpha2-adrenoceptors.
abstract: The physiological and pharmacological actions of norepinephrine (NE) on neurons of the intermediate subnucleus of the lateral septum (LSI) were examined using intracellular recordings in rat brain-slices. Bath-applied NE inhibited 72.5%, excited 5.5% and had no effect on 22% of LSI neurons tested; this study focused on the inhibitory effects of NE. In current clamp recordings, 100 microM NE produced a hyperpolarization of 10.82+/-0.72 mV (n=84) with a decrease in input resistance. In voltage-clamp, NE produced a direct, post-synaptic outward current of 206.8+/-22 pA (n=37) with a 64. 3+/-4.9% increase in input conductance (IC50-17.7+/-4 microM). The NE-induced inhibition was mimicked by the alpha2-agonist, UK14,304, but not by the alpha1- or beta-adrenoceptor agonists. The alpha2-agonist, clonidine, had a weak effect in LSI neurons. Interestingly, the magnitude of the UK14,304-induced response varied between cells (ranging from 29.5 to 320% of the maximal NE inhibition), possibly suggesting the involvement of alpha2A-(high affinity for UK14,304) and non-alpha2A (low affinity for UK14,304) adrenoceptor subtypes. While the alpha2-antagonists, yohimbine, rauwolscine and idazoxan blocked NE-induced inhibition in all neurons tested, the prototypical alpha1-antagonist, prazosin produced a variable degree of block (9-58%), further indicating the possible involvement of alpha2A (prazosin-insensitive) and non-alpha2A (prazosin-sensitive) receptors. However a lack of more selective pharmacological tools precludes definitive classification of the alpha2-receptor-mediated responses into different subtypes. The alpha2-receptor-mediated current in LSI neurons displayed Ba2+-sensitive inward rectification, reversed polarity near EK and was sensitive to external K+. In conclusion, NE inhibits LSI neurons via alpha2-adrenoceptor subtypes.
authors.affiliation: Department of Psychiatry, CMHC 306, Yale University School of Medicine and the Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Alreja
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012688:Septum Pellucidum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D001464:Barium; D011188:Potassium; D009638:Norepinephrine