Understanding the central mechanisms controlling eating behavior is important for understanding how the nervous system may contribute to the eating and body weight disorders common in Western society. Evidence implicates the lateral hypothalamus (LH) as a key site in the neural control of food intake. This project will examine the cellular mechanisms by which melanin-concentrating hormone (MCH), a peptide produced almost exclusively by LH neurons, participates in the control of eating behavior using the rat as a model system. Specifically, the anorectic effects of MCH will be tested in vivo, the determine which LH sites are most sensitive to the effect of MCH, and the time of the photoperiod in which MCH maximally reduces eating. The effects of MCH in rats feeding in response to the onset of the dark cycle, food deprivation, or LH glutamate receptor stimulation (all of which induce eating ) will be tested to determine conditions in which MCH might play a role as a physiological mediator of eating suppresion. The in vitro brain slice preparation will be used to address the effects of MCH on glutamatergic and GABAergic synaptic transmission in the LH, with an aim to identifying the cellular mechanisms by which MCH in the LH affects feeding. In addition, interactions of MCH with the feeding-stimulatory peptide neuropeptide Y will be examined in LH neurons in vitro, along with the possible intracellular mediators of MCH's effects on synaptic transmission. Given the almost exclusive localization of MCH to LH neurons, this work may have unusual potential to lead to the development of powerful and specific treatments for eating disorders.
