Chronic cold exposure increases RGS7 expression and decreases alpha(2)-autoreceptor-mediated inhibition of noradrenergic locus coeruleus neurons.
Chronic stress exposure alters the central noradrenergic neurons originating from the locus coeruleus (LC). Previously, we demonstrated that evoked increases in the firing rate of LC neurons and their release of norepinephrine are enhanced following chronic cold exposure. In the present studies, we tested the hypothesis that reduced feedback inhibition of LC neurons might underlie these alterations in LC activity by examining the effect of alpha(2)-autoreceptor stimulation on LC activity in chronically stressed rats using in vivo and in vitro single unit recordings. Given that regulators of G-protein signaling (RGS) proteins can impact the coupling of alpha(2)-autoreceptors to downstream signaling cascades, we also explored the expression of several RGS proteins following chronic stress exposure. We observed that the alpha(2)-autoreceptor-evoked inhibition of LC neurons was reduced and that the expression of RGS7 was increased following chronic stress exposure. Finally, we demonstrated that intracellular administration of RGS7 via patch clamp electrodes mimicked the stress-induced decrease in clonidine-evoked autoreceptor-mediated inhibition. These novel data provide a mechanism to explain how chronic stress-induced alterations in receptor coupling can result in changes in alpha(2)-autoreceptor control of noradrenergic function throughout the central nervous system, potentially leading to alterations in anxiety-related behaviors, and may suggest novel therapeutic targets for the treatment of mood and anxiety disorders.
Jedema
Hank P
HP
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15261, USA. Jedema@pitt.edu
Gold
Stephen J
SJ
Gonzalez-Burgos
Guillermo
G
Sved
Alan F
AF
Tobe
Ben J
BJ
Wensel
Theodore
T
Grace
Anthony A
AA
D000818:Animals; D017660:Autoreceptors / Q000378:metabolism; D015153:Blotting, Western; D003080:Cold Temperature; D004594:Electrophysiology; D015870:Gene Expression; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D020710:RGS Proteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013315:Stress, Psychological / Q000503:physiopathology*; D013995:Time
D017660:Autoreceptors; D020710:RGS Proteins; D018341:Receptors, Adrenergic, alpha-2; C115771:Rgs7 protein, rat; D009638:Norepinephrine