The κ opioid receptor and food intake

Morley, John E.; Levine, Allen S.; Kneip, J.; Grace, Martha K.; Zeugner, H.; Shearman, Gary T.

doi:10.1016/0014-2999(85)90234-1

Cited by 49 publications

(10 citation statements)

References 30 publications

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“…Both systemic and intracerebroventricular administration of general opioid receptor antagonists reduce food intake and body weight in rodent models, including genetically obese Zucker and diet-induced obese rats (4 -8). Pharmacological studies have demonstrated that bothand -specific antagonists can reduce both spontaneous and deprivation-induced feeding in rodents (9,10). In particular, the KOR antagonist nor-binaltorphimine showed robust reductions in the intake of palatable diets high in fat or sucrose (11,12).…”

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κ‐Opioid receptors control the metabolic response to a high‐energy diet in mice

et al. 2009

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General opioid receptor antagonists reduce food intake and body weight in rodents, but the contributions of specific receptor subtypes are unknown. We examined whether genetic deletion of the kappa-opioid receptor (KOR) in mice alters metabolic physiology. KOR-knockout (KO) and wild-type (WT) mice were fed a high-energy diet (HED) for 16 wk. KO mice had 28% lower body weight and 45% lower fat mass when compared to WT mice fed an HED. No differences in caloric intake were found. An HED reduced energy expenditure in WT mice, but not in KO mice. KOR deficiency led to an attenuation of triglyceride synthesis in the liver. Malonyl CoA levels were also reduced in response to an HED, thereby promoting hepatic beta-oxidation. Glycemic control was also found to be improved in KO mice. These data suggest a key role for KORs in the central nervous system regulation of the metabolic adaptation to an HED, as we were unable to detect expression of KOR in liver, white adipose tissue, or skeletal muscle in WT mice. This study provides the first evidence that KORs play an essential physiological role in the control of hepatic lipid metabolism, and KOR activation is a permissive signal toward fat storage.-Czyzyk, T. A., Nogueiras, R., Lockwood, J. F., McKinzie, J. H., Coskun, T., Pintar, J. E., Hammond, C., Tschöp, M. H., Statnick, M. A. kappa-Opioid receptors control the metabolic response to a high-energy diet in mice.

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κ‐Opioid receptors control the metabolic response to a high‐energy diet in mice

et al. 2009

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“…Some of these effects are stereospecific (Morley et al 1985) and reversible by naloxone (Jackson and Sewell 1984). In addition, the kappa receptor sites have been reported to be distributed throughout the rat brain, in gustatory and feeding areas (Lynch et al 1985) and central injection of dynorphin, the endogenous ligand for these sites (Chavkin et.…”

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An observational analysis of the effect of the selective kappa opioid agonist, U-50,488H, on feeding and related behaviours in the rat

Jackson

Cooper

1986

Psychopharmacology

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The behaviour of partially pre-satiated rats consuming a sweet palatable food and treated with either vehicle or the specific kappa receptor agonist U-50,488H (0.1-3 mg/kg) was recorded on videotape. Analysis revealed that the hyperphagia induced by the kappa agonist (0.3-3 mg/kg) resulted from an increase in the duration of feeding and not from an increase in the local rate of eating. The increase in duration was due, in turn, to a greater frequency of bouts of feeding. The kappa agonist also increased the latency to the final feeding bout. The effect of U-50,488H was consistent with de-satiation, so that the increase in feeding duration was in evidence from the start of the test period, while the temporal pattern of later satiation was preserved but lagged behind that of control animals. At the largest dose, other recorded activities (rearing, locomotor activity, grooming) were suppressed, with a marked increased in inactivity. At the lowest dose (0.1 mg/kg) there was a significant increase in grooming behaviour. The results are discussed with reference to an hypothesis of opioid function in the control of food intake.

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“…Naloxone antagonizes mu receptors more effectively than kappa receptors (e.g., Martin et al 1976;Sawynok et al 1979;Zukin and Zukin 1981 ;Pasternak and Wood 1986). Thus, the differences in sensitivity to naloxone antagonism of morphine and EKC hyperphagia suggest different opioid receptor mechanisms, and support kappa receptor modulation of some forms of opioid-induced feeding (Morley et al 1983(Morley et al , 1985Cooper et al 1985).…”

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confidence: 99%

“…Other opiate agonists also increase food intake (see review: Morley et al 1983). The receptor mechanisms of these agents are not clear, although specific receptor subtypes have been proposed (e.g., kappa: Morley et al 1983Morley et al , 1985Cooper et al 1985). Using previously reported feeding paradigms, we compared the actions of naloxone and naloxonazine on opioid-induced feeding following administration of morphine, EKC, dynorphin and DADL.…”

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Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine

et al. 1988

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The high-affinity mu-1 opioid binding site has been implicated in some opioid responses (e.g., supraspinal analgesia) but not others (e.g., respiratory depression) by comparing the actions of naloxone, a short-acting, non-selective antagonist, and naloxonazine, an irreversible and selective mu-1 antagonist. The mu-1 site has been implicated in the opioid component modulating free feeding and deprivation-induced feeding, but not glucoprivic feeding. The present study compared naloxone and naloxonazine antagonism of hyperphagia induced by morphine, ethylketocyclazocine (EKC), dynorphin and d-ala2,d-leu5-enkephalin (DADL) in rats. Morphine produced a dose-dependent (0.01-5 mg/kg) hyperphagia in mildly food-deprived rats that was blocked by naloxone (0.01-10 mg/kg). Naloxonazine (10 mg/kg) shifted the morphine hyperphagia dose-response curve to the right. These effects could not be fully accounted for by the intrinsic hypophagic properties of these antagonists. EKC produced a dose-dependent (0.5-5 mg/kg) hyperphagia which was blocked by naloxone (10 mg/kg) only at low effective EKC doses. Naloxonazine (10 mg/kg) failed to affect EKC hyperphagia. Naloxone, but not naloxonazine also blocked dynorphin and DADL hyperphagia. These results indicate that feeding induced by opiate and opioid agonists are differentially mediated by the mu-1 and other opioid binding sites; these data contrast with the modulation by the mu-1 site of the supraspinal analgesia induced by each of these agonists.

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The κ opioid receptor and food intake

Cited by 49 publications

References 30 publications

κ‐Opioid receptors control the metabolic response to a high‐energy diet in mice

κ‐Opioid receptors control the metabolic response to a high‐energy diet in mice

An observational analysis of the effect of the selective kappa opioid agonist, U-50,488H, on feeding and related behaviours in the rat

Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine

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