Corticotropin-releasing factor: putative neurotransmitter in the noradrenergic nucleus locus ceruleus.
The effects of hemodynamic stress produced by i.v. infusion of nitroprusside on discharge characteristics of noradrenergic locus ceruleus (LC) neurons were compared to those produced by central administration of corticotropin-releasing factor (CRF). Like CRF, both nitroprusside infusion and blood volume withdrawal increased LC spontaneous discharge. Additionally, nitroprusside disrupted the response of LC cells to repeated sciatic nerve stimulation in a manner similar to CRF. The neuronal effects of nitroprusside were prevented by prior administration of a CRF antagonist, alpha helical CRF9-41, but not by dexamethasone, which blocks CRF release into the hypophysial portal circulation. These results suggest that LC activation by hemodynamic stress is mediated by neuronal CRF release onto LC neurons. alpha Helical CRF9-41 had no effect on the magnitude or timecourse of nitroprusside-elicited hypotension, suggesting that LC activation by nitroprusside is not important for maintaining hemodynamic homeostasis. Finally, chronic administration of desmethylimipramine (DMI) attenuated the response of LC cells to nitroprusside, but not to CRF, suggesting that antidepressant therapy may inhibit stress-induced CRF release. This study supports the concept that CRF serves as a neurotransmitter in the LC in the initiation of stress responses.
Valentino
R J
RJ
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D018377:Neurotransmitter Agents; D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine