Eating Elicited by Orexin-A, But Not Melanin-Concentrating Hormone, Is Opioid Mediated

Clegg, Debbie J.

doi:10.1210/en.143.8.2995

Cited by 89 publications

(74 citation statements)

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“…Clegg et al reported that i.c.v. injection of orexin-A and -B increased food intake for 1 h, and that the effects were inhibited completely by intraperitoneal injection of naloxone, an antagonist of the opioid receptor (2). Furthermore, i.c.v.…”

Section: Resultsmentioning

confidence: 93%

POMC and orexin mRNA expressions induced by anticipation of a corn-oil emulsion feeding are maintained at the high levels until oil ingestion

et al. 2006

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We investigated the gene expression dynamics of several hypothalamic neuropeptides associated with appetite regulation when rats are anticipating being fed a corn-oil emulsion. For 5 days at the same hour each day, rats were fed 5% corn oil emulsifi ed with 0.3% xanthan gum or the vehicle for 20 min. On Day 6, the 5% corn oil emulsion or the vehicle (Vehicle) was presented to the rats, some of which (Oil-intake) were allowed to eat it and some of which (Oil-anticipation) were kept from eating it. Despite waiting a corn-oil, the mRNA levels of proopiomelanocortin (POMC), a β-endorphin precursor, and orexin showed increases, and high levels of mRNAs of POMC and orexin were maintained for 30 min after the corn-oil was placed before the rats, and only gradually decreased through 150 min. However, the mRNA levels of POMC and orexin in the hypothalamus were decreased within 30 min after starting to ingest the corn-oil emulsion. These results suggest that POMC and orexin mRNA expression was induced by the anticipation in rats after learning the palatability of 5% corn oil emulsion, and the induced mRNA expression based on the anticipation was maintained for at least for 30 min as the rats eagerly waited for ingestion.Obesity resulting from excessive energy ingestion is a serious health issue. Despite warnings about excessive ingestion of high-fat foods, there currently appears to be no decrease in consumption of such foods (3,11,18,22). It is thought that many mammals prefer to consume high-fat foods due to their pleasant taste, flavor, and texture. In short-term 2-bottle choice tests, mice prefer vegetable oils to sucrose, itself a highly palatable substance (20). In addition, conditioned place preference (CPP) tests have demonstrated a reinforcing effect of corn oil on mice (6). In comparison to rats fed on regular chow diets, rats fed on a high-fat diet show a greater food intake and became overweight as a result (1). Understanding why mammals, including humans, prefer high-fat foods will provide important information for regulating oil ingestion and thus maintaining good health.Several neuropeptides produced in the hypothalamus mediate feeding behavior. These include proopiomelanocortin (POMC), produced in arcuate nucleus of hypothalamus, and physiologically co-active peptides like beta-endorphin, adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH) (4, 17). We discovered that betaendorphin, an opioid peptide, is released just after dietary oil ingestion in rats (12). Moreover, the gene expression of POMC (a precursor of beta-endorphin) increased just before dietary oil ingestion (12).

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Section: Resultsmentioning

confidence: 93%

POMC and orexin mRNA expressions induced by anticipation of a corn-oil emulsion feeding are maintained at the high levels until oil ingestion

et al. 2006

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“…MCH administration stimulated the consumption of a high-fat diet equally to that of low-fat diet. Further, the effect of MCH on food intake was found to be independent of the opioid system, which is thought to be involved in signaling the relative palatability of food (Clegg et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

The regulation of alcohol intake by melanin-concentrating hormone in rats

Duncan

Rider

Jandacek

et al. 2006

Pharmacology Biochemistry and Behavior

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Given into the brain, melanin-concentrating hormone (MCH) increases alcohol consumption, but the mechanism and physiological relevance of this effect are unclear. We hypothesized that endogenous MCH will enhance alcohol drinking and that MCH increases alcohol's reinforcing properties. An MCH receptor 1 (MCHR1) antagonist, or saline was administered centrally alone, or preceding MCH or saline to rats trained to drink 10% alcohol using sucrose fading. Blocking MCHR1 neither reduced alcohol intake (saline = 0.4 ± 0.1g, 30 μg MCHR1 antagonist = 0.4 ± 0.1 g/kg alcohol), nor attenuated MCH-induced alcohol drinking (MCHR1 antagonist/saline = 0.7 ± 0.1 g/kg, MCHR1 antagonist/MCH = 0.9 ± 0.1 g/kg alcohol). Another cohort of rats was trained to lever press for alcohol on a progressive ratio schedule. MCH or saline was administered centrally and lever presses were measured. MCH had no effect prior to the break point, but increased total responding during the session (saline = 87.2 ± 32.0, MCH = 315.4 ± 61.0 presses). In conclusion, these data suggest that MCH augments alcohol drinking partly by enhancing the drug's reinforcing value. Further, endogenous MCH does not seem to regulate alcohol drinking, however because the antagonist failed to attenuate MCH-induced alcohol intake this conclusion is tentative.

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“…These findings indicate that the dopaminecontaining neurons in the midbrain VTA, which has a high density of -opioid receptors, play a critical role in the rewarding effects of -opioids. It has been reported that endogenous opioids are needed for orexin-induced feeding (Clegg et al, 2002). It is of interest to note that prepro-orexin knock-out mice develop attenuated morphine-induced physical dependence and withdrawal (Georgescu et al, 2003), suggesting a possible interaction between orexins and opioids.…”

Section: Discussionmentioning

confidence: 99%

Direct Involvement of Orexinergic Systems in the Activation of the Mesolimbic Dopamine Pathway and Related Behaviors Induced by Morphine

et al. 2006

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In this study, we investigated the role of orexinergic systems in dopamine-related behaviors induced by the -opioid receptor agonist morphine in rodents. Extensive coexpression of tyrosine hydroxylase with orexin receptors was observed in the mouse ventral tegmental area (VTA). The levels of dopamine and its major metabolites in the nucleus accumbens were markedly increased by the microinjection of orexin A and orexin B into the VTA. The subcutaneous morphine-induced place preference and hyperlocomotion observed in wild-type mice were abolished in mice that lacked the prepro-orexin gene. An intra-VTA injection of a selective orexin receptor antagonist SB334867A [1-(2-methylbenzoxazol-6-yl)-3-[1.5]naphthyridin-4-yl urea] significantly suppressed the morphine-induced place preference in rats. Furthermore, the increased level of dialysate dopamine produced by morphine in the mouse brain was significantly decreased by deletion of the prepro-orexin gene. These findings provide new evidence that orexin-containing neurons in the VTA are directly implicated in the rewarding effect and hyperlocomotion induced by morphine through activation of the mesolimbic dopamine pathway in rodents.

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Eating Elicited by Orexin-A, But Not Melanin-Concentrating Hormone, Is Opioid Mediated

Cited by 89 publications

References 0 publications

POMC and orexin mRNA expressions induced by anticipation of a corn-oil emulsion feeding are maintained at the high levels until oil ingestion

POMC and orexin mRNA expressions induced by anticipation of a corn-oil emulsion feeding are maintained at the high levels until oil ingestion

The regulation of alcohol intake by melanin-concentrating hormone in rats

Direct Involvement of Orexinergic Systems in the Activation of the Mesolimbic Dopamine Pathway and Related Behaviors Induced by Morphine

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