Bulimia and anorexia are severe mental health problems in the U.S.A. Overweight and underweight can also be deleterious to people's physical health.To help lay the groundwork for effective treatment, the investigator proposes to study the neural mechanisms that control feeding reward and aversion. Five projects will explore the basic neurochemistry of limbic structures that modulate the positive and negative reinforcement of eating. The technique to be used is microdialysis, which the investigator has developed for use in freely moving animals. Experiment 1 focuses on dopamine (DA) in the nucleus accumbens (NAC) where this neurochemical is sufficient for positive reinforcement of operant behavior,including feeding. This will be a reductionistic analysis measuring DA release (a) during food procurement effort, (b) during a meal, (c) with food taste alone, (d) with food in the stomach alone, then (f) with taste and gastric factors associated through experience to teach a learned taste preference or (f) a learned taste aversion; thus he will measure learned neurotransmitter release. Experiment 2 will follow up pilot evidence showing that acetylcholine (ACh) in the NAC is released by a meal, inhibits feeding and induces food aversion. Experiment 3 will investigate the interaction of DA and ACh in the NAC and a possible role in mediating opponent processes. Experiment 4 shifts to the hypothalamus to examine whether hypothalamic neurotransmitters that are known to control feeding also control the release of DA andACh in the NAC, thus controlling the reinforcing aspects of food. Experiment 5 will study neuropeptide Y and cholecystokinin infused into the PVN basedon evidence that they work in synergy with NE and 5HT to control specific aspects of feeding. Experiment 6 focuses on insulin, because it is tightly linked to body weight and acts locally in the medial hypothalamus (MH) to promote satiety.
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