Corticotropin-releasing factor induces differential behavioral and cardiovascular effects after intracerebroventricular and lateral hypothalamic/perifornical injections in rats

Abstract

The contribution of the lateral hypothalamic/perifornical (LH/PFx) area in mediating central effects of corticotropin-releasing factor (CRF) on cardiovascular and behavioral activity was assessed by monitoring blood pressure, heart rate and behavioral responses for a 45-min period after injections of various doses of CRF into the LH/PFx region or the lateral cerebral ventricle (intracerebroventricular, i.c.v.) in conscious, unrestrained rats in a familiar environment. After LH/PFx injection, CRF (3 and 30 ng) dose-dependently induced behavioral activation, predominantly consisting of grooming, eating and locomotor activity. Concomitantly, dose-related increases in mean arterial pressure (delta MAP) and heart rate (delta HR) were observed. Increases in MAP and HR following injection of 3 ng CRF were associated with the paroxysmal occurrence of behavioral activation and as such superimposed on CRF-induced elevation of baseline MAP and HR. Thirty nanograms CRF given i.c.v. produced grooming behavior similar to that observed after the same dose injected into the LH/PFx region, but failed to induce significant changes in cardiovascular concomitants. Rats receiving 100 ng CRF i.c.v., showed a significant increase in behavioral activity, respective to rats treated with 30 ng CRF in the LH/PFx, the tachycardiac responses, however, being similar in these groups. Both doses of CRF i.c.v. failed to induce significant delta MAP. The effects of CRF on cardiovascular and behavioral activity were more marked when the peptide was injected into the caudal part of the LH than those measured after administration into the rostral LH. Similarly, injections of CRF around or dorsal to the fornix (PFx) were more effective than those located ventrally to it. This site specificity of CRF-evoked responses was reflected in differential time response relations of the various effects. In summary, when i.c.v. is the route of administration, a higher dose of CRF is required to induce autonomic and behavioral responses similar to those elicited by CRF injected into the LH/PFx. The cardiovascular and behavioral effects of LH/PFx-CRF indicate that this region may be an important site for central CRF to produce stress-related autonomic and behavioral responses. In addition, the CRF-induced effects, both in magnitude and onset, show site specificity, the caudal LH and perifornical area being more responsive to the peptide than the rostral LH and the area ventral to the Fx. As CRF-evoked behavioral activation does not necessarily coincide with changes in MAP and HR, our data suggest a dissociation of the peptide's central actions to influence behavioral and autonomic responses.