REGULATION OF A PUTATIVE NEUROTRANSMITTER EFFECT OF CORTICOTROPIN-RELEASING FACTOR - EFFECTS OF ADRENALECTOMY

This study tested the hypothesis that endogenous glucocorticoids regul ate a putative neurotransmitter function of corticotropin-releasing fa ctor (CRF) in the locus coeruleus (LC). LC spontaneous discharge and a ctivation by intracerebroventricularly administered CRF, hypotensive c hallenge, sciatic nerve stimulation, and carbachol were compared in ad renalectomized and sham-operated halothane-anesthetized rats. LC spont aneous discharge was higher in adrenalectomized versus sham-operated r ats. Intracoerulear microinfusion of a CRF antagonist decreased LC dis charge rates of adrenalectomized rats to rates comparable with those o bserved in sham-operated rats but had no effect in sham-operated rats. The CRF dose-response curve was shifted in a complex manner in adrena lectomized rats, suggesting that a proportion of CRF receptors were oc cupied before CRF administration, and low doses of CRF were additive. Higher doses of CRF produced effects that were greater than predicted by simple additivity. Hypotensive challenge increased LC discharge rat es of adrenalectomized rats by a magnitude greater than that predicted on the basis of additivity. In contrast, LC responses to carbachol an d sciatic nerve stimulation were similar in both groups. The results s uggest that adrenalectomy enhances tonic and stress-induced CRF releas e within the LC and also alters postsynaptic sensitivity of LC neurons to CRF. Because adrenalectomy also alters release of neurohormone CRF , the present study suggests that CRF actions as a neurohormone and as a neurotransmitter in the LC may be co-regulated. Such parallel regul ation may underlie the coexistence of neuroendocrine and noradrenergic dysfunctions in stress-related psychiatric disorders.