INTERACTION BETEEW OREXIN-A AND MESOLIMBIC DOPAMINE IN PALATABLE FOOD CONSUMPTION

Several studies reported that orexinergic neurons in the lateral hypothalamus (LH) are involved in motivated behavior for drugs of abuse as well as natural rewards. In particular it has been observed that administration of orexin A (OrxA) stimulates food consumption, and orexin signaling in VTA is implicated in the intake of high-fat food. On the other hand in the VTA are located dopaminergic neurons that project to the nucleus accumbens (NAc) shell, an area in which the dopamine (DA) plays a key role in the responsiveness to the rewarding properties of food as well as of drugs of abuse. The aim of our study was to investigate if there is any cooperation between the OrxA and the DA released in the NAc shell. We investigated by brain microdialysis the responsiveness of NAc shell DA in food consumption after intravenous administration of OrxA encapsulated in different targeted and not-targeted stealth liposomes. OrxA per se produced an increase of DA in the NAc shell and strengthened the DA responsiveness in this area to sucrose pellets consumption. OrxA administration also increased the number of eaten pellets. These effects on DA transmission and feeding were affected by the antagonist of the OxR1 (SB 334867). We can hypothesize that the strengthening of DA response during food consumption exerted by OrxA administration could increase the rewarding properties of food and could be one of the mechanisms that underlie food addiction. These findings could suggest new targets for a new treatment of eating disorders. Study supported by Regione Autonoma della Sardegna