Chronic cold exposure potentiates CRH-evoked increases in electrophysiologic activity of locus coeruleus neurons

Background: Chronic stress exposure can produce sensitization of norepineph rine release in the forebrain in response to subsequent stressors, Furtherm ore, the increase in norepinephrine release in response to the stress-relat ed peptide corticotropin-releasing hormone (CRH) is potentiated by prior ch ronic stress exposure. To explore possible mechanisms underlying these alte rations in norepinephrine release, we examined the effect of chronic stress on the electrophysiologic activity of locus coeruleus (LC) neurons in resp onse to centrally applied CRH. Methods: Single-unit recordings of LC neurons in halothane-anesthetized mts were used to compare the effect of intraventricular administration of CRH (0.3-3.0 mug) in control and previously cold-exposed (2 weeks at 5 degreesC ) rats. Results: The CRN-evoked increase in LC neuron activity was enhanced followi ng chronic cold exposure, without alteration in basal activity of LC neuron s. The enhanced CRH-evoked activation was apparent at higher doses of CRH b ur not at lower ones, resulting in an increased slope of the dose-response curve for CRH in previously cold-exposed rats. Conclusions: These data, in combination with previous data, suggest that th e sensitivity of LC neurons to excitatory inputs is increased following chr onic cold exposure. The altered functional capacity of LC neurons in rats a fter continuous cold exposure may represent an experimental model to examin e the role of central noradrenergic neurons in anxiety and blood disorders. (C) 2001 Society of Biological Psychiatry.