Modulation of central nervous system actions of corticotropin-releasing factor by dynorphin-related peptides

Corticotropin-releasing factor (CRF) and dynorphin-related peptides are co-localized within a subset of hypothalamic neurons suggesting the possibility of their co-release. Therefore, studies were performed in conscious unrestrained rats to examine whether dynorphin-related peptides modify the central nervous system (CNS) actions of CRF on sympathetic nervous activity and cardiovascular function. Intracerebroventricular (i.c.v.) administration of dynorphin A1-8 (0.1 and 1.0 nmol) did not alter arterial pressure (AP) or heart rate (HR). I.c.v. injection of dynorphin A1-13 (0.1, 0.3 and 1.0 nmol) produced transient elevations of HR but did not significantly affect AP. I.c.v. administration of dynorphin A1-17 (0.1, 0.3 and 1.0 nmol) elicited delayed (10-15 min) and transient elevations of AP and HR. CRF (0.15 nmol, i.c.v.) produced immediate and sustained elevations of AP, HR and plasma catecholamine levels. Upon simultaneous administration, 0.1 nmol of dynorphin A1-17, but not 0.1 nmol of dynorphin A1-8 or dynorphin A1-13, markedly attenuated CRF-induced elevations of AP, HR, and plasma catecholamine levels. The results suggest that selected dynorphin-related peptides may modify the CNS actions of CRF.