The role of nitric oxide signaling in reward induced by ghrelin and alcohol in mice

Abstract

Degree Project thesis, Programme in Medicine. TITLE: The role of nitric oxide signaling in reward induced by ghrelin and alcohol in mice. Abstract Ghrelin in known to regulate energy balance. Growing evidence on common mechanisms involved in ghrelin’s, alcohol’s as well as other drugs’ rewarding properties has been found. A nitric oxide signaling pathway has shown to be of importance for ghrelin induced feeding as well as the rewarding effects of morphine and cocaine. We therefore hypothesize that the rewarding properties of ghrelin and alcohol might involve the same signaling pathway. Alcohol addiction is a chronic relapsing brain disease with major costs for individuals, families as well as society. The current treatment has proven to be insufficient. A key feature in development of addiction is the activation of the brain’s reward system. The hunger hormone ghrelin has recently shown to be of importance for the rewarding properties of alcohol as well as other addictive drugs. Furthermore, alcohol and ghrelin has shown great neurochemical similarities, as well as having similar reward mechanisms. The nitric oxide involving reaction ending in a cGMP cascade is of importance for ghrelin induced feeding as well as the rewarding properties of cocaine and morphine. Therefore, the effects of the nitric oxide synthase inhibitor L-name on the rewarding properties of alcohol and ghrelin was studied. A model for reward measurement called Conditioned Place Preference (CPP) was used where half of the mice received L-name during conditioning and half received it acutely, after conditioning. Mice receiving L-name was compared to mice receiving vehicle (placebo) using an uncoupled T-test. L-name does not have any intrinsic rewarding effects. The rewarding effects of alcohol are not affected by L-name administration. Chronic administration of L-name induces a CPP in ghrelin conditioned mice. Thus suggesting a role for nitric oxide signaling mediating the rewarding properties of ghrelin. Taken together with ghrelin’s hunger stimulating effects, nitric oxide signaling proves to be of importance for binge eating.