NEUROPEPTIDE-Y AND SIGMA-LIGAND (JO-1784) ACT THROUGH A GI PROTEIN TO BLOCK THE PSYCHOLOGICAL STRESS AND CORTICOTROPIN-RELEASING FACTOR-INDUCED COLONIC MOTOR ACTIVATION IN RATS

The effects of neuropeptide Y and sigma ligands (d-NANM and JO 1784) on corticotropin-releasing factor (CRF) and psychological stress-stimulated caecal and colonic motility were evaluated by electromyography in rats equipped with chronically implanted electrodes on the caecum and proximal colon and a small catheter into the right lateral ventricle of the brain. Exposure to a psychological stress for 30 min increased significantly (P < 0.05) the frequency of caecal and colonic spike bursts, an effect which was mimicked by intracerebroventricular administration of CRF (300 ng/kg). Injected intracerebroventricularly, 30 min prior to the psychological stress or intracerebroventricular administration of CRF, neuropeptide Y (150 ng/kg) abolished the excitatory effect on caeco-colonic motility. Similarly, prior administration of d-NANM (100 ng/kg) and JO 1784 (50 ng/kg) abolished the caeco-colonic hypermotility induced by psychological stress and intracerebroventricular injection of CRF. Four days after intracerebroventricular administration of pertussis toxin (150 ng/kg), both neuropeptide Y and JO 1784, when administered centrally, were unable to antagonize the stress-induced hyperkinesia. It is concluded that central administration of neuropeptide Y and delta ligands abolish the stimulatory effects of psychological stress on caeco-colonic motility by blocking the pathways by which CRF activates the motility, through a common mechanism involving a pertussis toxin-sensitive Gi protein.