Anorexigenic cocaine- and amphetamine-regulated transcript peptide intensifies fear reactions in rats

An increasing number of appetite-regulating peptides are being discovered. The list of regulators inhibiting food intake is considerably longer than t hat of appetite stimulators, In many cases, the peptides inhibiting food in take facilitate fear reactions, whereas the majority of the agents reducing anxiety responses stimulate appetite. Cocaine- and amphetamine-regulated t ranscript (CART) cDNA was isolated from hypothalamic libraries and CART was reported to inhibit food intake and to mediate the anorectic effects of le ptin, Here, we show that the active core fragment of CART (CART(89-103), 0. 04-5.0 nmol) injected into lateral cerebral ventricle not only inhibits foo d intake, but also causes a dose-dependent increase in anxiety-like reactio ns in elevated plus-maze test. Intracerebroventricular administration of CA RT(82-103) (0.04-5.0 nmol) did not inhibit water intake and did not affect spontaneous locomotor activity in the open field test ruling out unspecific effects of the peptide. Our results suggest that CART could be an endogeno us factor in the brain mediating the effects of stress on appetite. (C) 200 0 Elsevier Science B.V. All rights reserved.