Intraperitoneal corticotropin-releasing factor and urocortin induce Fos expression in brain and spinal autonomic nuclei and long lasting stimulation of colonic motility in rats

Abstract

CRF injected intraperitoneally (i.p.) stimulates colonic motor function and induces Fos expression in colonic myenteric neurons. We investigated central and spinal Fos expression and changes in colonic motility in response to i.p. injection of CRF and urocortin. Ovine CRF 9–33 that is devoid of intrinsic activity at the CRF receptors, was used as control peptide. Myoelectrical activity was monitored for 1 h before and after peptide injection (10 μg/kg, i.p.) in conscious non fasted rats with chronically implanted intraparietal electrodes in the cecum and proximal colon. Brain and lumbosacral spinal cord were processed for Fos immunohistochemistry at 1 h postinjection. CRF and urocortin elicited defecation and a new pattern of ceco–colonic clustered spike bursts that peaked within 15 min and lasted for the 1 h experimental period while CRF 9–33 did not modify baseline myoelectrical activity and defecation. CRF increased significantly Fos expression in the central nucleus of the amygdala (lateral part), parabrachial nucleus (external lateral subnucleus), area postrema, nucleus tractus solitarius, locus coeruleus, paraventricular nucleus of the hypothalamus, the intermediolateral column and area I–VII, X at the L6–S1 level of the spinal cord by 11-, 6.5-, 5.3-, 5.0-, 4.7-, 2.7- and 1.4-fold, respectively compared with i.p. CRF 9–33 injected rats that had little Fos expression. Urocortin induced a similar pattern of Fos response in the brain and the spinal cord. These results indicate that i.p. CRF and urocortin induce a peptide specific activation of brain nuclei receiving viscerosensory inputs and involved in autonomic circuitries whose effector limbs may impact on visceral function.