Melanocortin receptor agonist melanotan-II microinjected in the nucleus accumbens decreases appetitive and consumptive responding for food

Rationale.—Obesity is a major health problem worldwide. An understanding of the factors that drive feeding behaviors is key to the development of pharmaceuticals to decrease appetite and consumption. Proopiomelanocortin (POMC), the melanocortin peptide precursor, is essential in the regulation of body weight and ingestive behaviors. Deletion of POMC or impairment of melanocortin signaling in the brain results in hyperphagic obesity. Neurons in the hypothalamic arcuate nucleus produce POMC and project to many areas including the nucleus accumbens (NAcc), which is well established in the rewarding and reinforcing effects of both food and drugs of abuse.

Objective.—These studies sought to determine the role of melanocortins in the NAcc on consumption of and motivation to obtain access to standard rodent chow.

Methods.—Male, C57BL/6J mice were microinjected bilaterally into the NAcc (100 nl/side) with the melanocortin receptor 3/4 agonist melanotan-II (MT-II; 0.1, 0.3, and 1 nmol), and ingestive behaviors were examined in both home cage and operant food self-administration experiments. In addition, the ability of MT-II in the NAcc to produce aversive properties or affect metabolic rate were tested.

Results.—MT-II injected into the NAcc significantly decreased consumption in both home cage and operant paradigms, and furthermore decreased appetitive responding to gain access to food.

There was no development of conditioned taste avoidance or change in metabolic parameters following anorexic doses of MT-II.

Correspondence and current address: Amanda L. Sharpe, Ph.D. University of Oklahoma Health Science Center 1110 N. Stonewall

Ave, CPB 335 Oklahoma City, OK 73117 Amanda-Sharpe@ouhsc.edu, Phone 405.271.6593. Declaration of interests: The authors have no conflicts of interest to disclose.

Author manuscript Neuropeptides. Author manuscript; available in PMC 2023 December 01.

Published in final edited form as: Neuropeptides. 2022 December ; 96: 102289. doi:10.1016/j.npep.2022.102289.

Conclusions.—MT-II in the NAcc decreased both the motivation to eat and the amount of food consumed without inducing an aversive state or affecting metabolic rate, suggesting a role for melanocortin signaling in the NAcc that is selective for appetite and satiety without affecting metabolism or producing an aversive state.

Keywords melanocortin receptor; feeding behavior; appetite; satiety; conditioned taste avoidance