Norepinephrine inhibits neurons of the intermediate subnucleus of the lateral septum via α 2-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 μM 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 (IC 50—17.7±4 μM). The NE-induced inhibition was mimicked by the α 2-agonist, UK14,304, but not by the α 1- or β-adrenoceptor agonists. The α 2-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 α 2A-(high affinity for UK14,304) and non-α 2A (low affinity for UK14,304) adrenoceptor subtypes. While the α 2-antagonists, yohimbine, rauwolscine and idazoxan blocked NE-induced inhibition in all neurons tested, the prototypical α 1-antagonist, prazosin produced a variable degree of block (9–58%), further indicating the possible involvement of α 2A (prazosin-insensitive) and non-α 2A (prazosin-sensitive) receptors. However a lack of more selective pharmacological tools precludes definitive classification of the α 2-receptor-mediated responses into different subtypes. The α 2-receptor-mediated current in LSI neurons displayed Ba 2+-sensitive inward rectification, reversed polarity near E K and was sensitive to external K +. In conclusion, NE inhibits LSI neurons via α 2-adrenoceptor subtypes.