Regulation of motivation for food by neuromedin U in the paraventricular nucleus and the dorsal raphe nucleus.

Abstract

BACKGROUNDMotivation for high-fat food is thought to contribute to excess caloric intake in obese individuals. A novel regulator of motivation for food may be Neuromedin U (NMU), a highly-conserved neuropeptide which influences food intake. Although these effects of NMU have primarily been attributed to signaling in the paraventricular nucleus of the hypothalamus (PVN), NMU has also been found in other brain regions involved in both feeding behavior and motivation. We investigate the effects of NMU on motivation for food and food intake, and identify the brain regions mediating these effects.METHODSThe motivational state for a particular reinforcer (e.g., high-fat food) can be assessed using a progressive ratio schedule of reinforcement under which an increasing number of lever presses are required to obtain subsequent reinforcers. Here, we have employed a progressive ratio operant responding paradigm in combination with an assessment of cumulative food intake to evaluate the effects of NMU administration in rats, and identify the brain regions mediating these effects.RESULTSWe found that peripheral administration of NMU decreases operant responding for high-fat food in rats. Evaluation of Fos-like immunoreactivity in response to peripheral NMU indicated the PVN and dorsal raphe nucleus (DRN) as sites of action for NMU. NMU infusion into either region mimics the effects of peripheral NMU on food intake and operant responding for food. NMU-containing projections from the lateral hypothalamus (LH) to the PVN and DRN were identified as an endogenous source of NMU.CONCLUSIONSThese results identify the DRN as a site of action for NMU, demonstrate that the LH provides endogenous NMU to the PVN and DRN, and implicate NMU signaling in the PVN and DRN as a novel regulator of motivation for high-fat foods.