Corticotropin-Releasing Factor: Evidence for a Neurotransmitter Role in the Locus ceruleus during Hemodynamic Stress

Abstract

Corticotropin-releasing factor (CRF) is localized in fibers in the noradrenergic nucleus locus ceruleus (LC) and alters LC discharge characteristics when administered centrally. To determine whether CRF functions as a neurotransmitter in the LC during stress, the effects of hemodynamic stress on LC discharge were compared to those of CRF. Hemodynamic stress elicited by intravenous nitroprusside infusion produced identical effects on LC spontaneous and sensory-evoked discharge as those reported for centrally administered CRF. Thus, nitroprusside increased LC spontaneous discharge rates, and disrupted LC discharge evoked by sensory stimuli such that the stimuli were less effective in producing phasic increases in LC discharge. The neuronal effects of nitroprusside were completely blocked by central administration of the CRF receptor antagonist, α helical CRF9–41, but not by pretreatment with dexamethasone which blocks stress-elicited hypophyseal CRF release. The present results confirm other reports of LC activation by stressors, and extend these studies by demonstrating that, in certain circumstances, this activation is dependent on endogenous CRF. This study supports the concept that CRF functions as a neurotransmitter in the LC in the initiation of stress responses.