Cocaine- and amphetamine-regulated transcript stimulates colonic motility via central CRF receptor activation and...

Many neuropeptides participating in the hypothalamic control of feeding behaviour and satiety have been shown to be additionally involved in the autonomic control of gastrointestinal (GI) functions. Recently, the neuropeptide cocaine- and amphetamine-regulated transcript (CART) has been indicated to function as an anorectic substance in the brain. In the present study we examine the hypothesis that CART is involved in the modulation of GI motility. Colonic transit time was measured after peripheral and central injection of CART in fed and freely moving Sprague-Dawley rats. Intracerebroventricular injection of synthetic CART (55-102) (190 pmol and 1.9 nmol per 10 microL and saline controls) decreased the colonic transit time of conscious rats up to 46%. In contrast, i.p. injection of CART (55-102) (1.9 nmol and 19 nmol kg(-1) BW and saline controls) had no effect on colonic motility. Central administration of a CRF receptor antagonist (2.8 nmol) prior to central CART administration antagonized the CART-induced stimulation of colonic transit. Pretreatment with the peripherally acting cholinergic antagonist atropin methyl nitrate (0.1 mg kg(-1) i.p.) blocked the stimulatory CART effect on colonic motor function. The results suggest that CART acts in the central nervous system to modulate behavioural motor function via a central CRF receptor-dependent mechanism and peripheral cholinergic pathways.