dynorphins and Hyperphagia

Compulsive overconsumption of reward characterizes disorders ranging from binge eating to drug addiction. Here, we provide evidence that enkephalin surges in an anteromedial quadrant of dorsal neostriatum contribute to generating intense consumption of palatable food. In ventral striatum, mu opioid circuitry contributes an important component of motivation to consume reward. In dorsal neostriatum, mu opioid receptors are concentrated within striosomes that receive inputs from limbic regions of prefrontal cortex. We employed advanced opioid microdialysis techniques that allow detection of extracellular enkephalin levels. Endogenous >150% enkephalin surges in anterior dorsomedial neostriatum were triggered as rats began to consume palatable chocolates. In contrast, dynorphin levels remained unchanged. Furthermore, a causal role for mu opioid stimulation in overconsumption was demonstrated by observations that microinjection in the same anterior dorsomedial quadrant of a mu receptor agonist ([D-Ala2, N-MePhe4, Gly-ol]-enkephalin; DAMGO) generated intense >250% increases in intake of palatable sweet food (without altering hedonic impact of sweet tastes). Mapping by "Fos plume" methods confirmed the hyperphagic effect to be anatomically localized to the anteromedial quadrant of the dorsal neostriatum, whereas other quadrants were relatively ineffective. These findings reveal that opioid signals in anteromedial dorsal neostriatum are able to code and cause motivation to consume sensory reward.

Topics: Animals; Brain Mapping; Cacao; Dynorphins; Eating; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Feeding Behavior; Hyperphagia; Neostriatum; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Signal Transduction

Palatability is one of the factors that regulates food and fluid intake and contributes to overconsumption in turn contributing to obesity. To elucidate the brain mechanisms of the palatability-induced ingestion, we explored the roles of six hypothalamic orexigenic neuropeptides, orexin, melanin-concentrating hormone (MCH), neuropeptide Y (NPY), agouti-related protein (AgRP), ghrelin and dynorphin, in the intake of a palatable solution, saccharin. Of the six peptides, intracerebroventricular (i.c.v.) administrations of orexin, MCH and NPY increased the intake of saccharin. Drinking of saccharin in turn elevated the mRNA levels of orexin and NPY, but not MCH. Pre-treatments of naloxone, an opioid antagonist, blocked the orexigenic effects of orexin and NPY. Specific gastric motor responses induced by central orexin-A and NPY are well known, however, MCH did not induce such responses. The i.c.v. administration of orexin-A facilitated gastric emptying. These results suggest that the overconsumption promoted by sweet and palatable tastes is attributed to the activation of orexigenic neuropeptides, such as orexin and NPY, and a downstream opioid system together with enhanced digestive functions.

Topics: Agouti-Related Protein; Animals; Appetite Regulation; Dynorphins; Feeding Behavior; Gastrointestinal Motility; Ghrelin; Hyperphagia; Hypothalamic Hormones; Injections, Intraventricular; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Male; Melanins; Neuropeptide Y; Neuropeptides; Orexins; Peptide Hormones; Pituitary Hormones; Rats; Rats, Wistar; RNA, Messenger; Sweetening Agents; Taste

Opioid involvement in regulating the intake of highly palatable diets was studied by examining the effect of feeding either a cornstarch-based diet (CHO) or a high fat diet containing sucrose (Fat/Sucrose) on hypothalamic opioid levels. Rats received either CHO ad libitum, Fat/Sucrose ad libitum, Fat/Sucrose pair-fed to the caloric intake of CHO, or Fat/Sucrose at 60% of ad libitum Fat/Sucrose intake. Animals receiving Fat/Sucrose ad libitum consumed more calories and gained more weight than animals receiving CHO (P < 0.001). Relative to CHO, ad libitum intake of Fat/Sucrose elevated proDynorphin mRNA levels in the arcuate and Dynorphin A1-17 levels in the paraventricular nucleus (PVN) (P < 0.05), but did not affect arcuate mRNA levels of proEnkephalin or proOpiomelanocortin (POMC), or PVN levels of Met-Enkephalin or beta-Endorphin. Pair-feeding the Fat/Sucrose diet to the level of intake of the CHO diet resulted in levels of proDynorphin and Dynorphin A1-17 that were similar in the two diet groups. Pair-feeding Fat/Sucrose reduced mRNA levels of proDynorpin, proEnkephalin and POMC, and Dynorphin A1-17 levels, relative to ad libitum feeding of Fat/Sucrose. Met-Enkephalin and beta-Endorphin were not affected by dietary treatment. Feeding Fat/Sucrose at 60% of ad libitum intake resulted in mRNA levels of proDynorphin, proEnkephalin and POMC, and Dynorphin A1-17 levels that were similar to those observed in CHO group. Hypothalamic Dynorphin A1-17 and proDynorphin mRNA levels are stimulated by feeding a highly palatable diet rich in fat and sucrose. The increased synthesis may be due in part to a palatability-induced overconsumption of calories. Caloric restriction of the same diet decreases mRNA levels of proDynorphin, proEnkephalin and POMC, as well as levels of Dynorphin A1-17.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Blotting, Northern; Diet; Dynorphins; Food Preferences; Hyperphagia; Hypothalamus; Male; Opioid Peptides; Paraventricular Hypothalamic Nucleus; Radioimmunoassay; Rats; Rats, Sprague-Dawley; RNA, Messenger; Taste; Weight Gain