Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine. 289 39

Two hypotheses have attempted to account for the abilities of opioid agonists and antagonists to respectively stimulate and inhibit food intake in rats. The first suggests that the opioid system selectively modulates fat intake, while the second suggest that the opioid system selectively alters intake of that macronutrient which the animal prefers. The present study evaluated these two hypotheses by examining total intake and individual macronutrient intake in either food-deprived (24 h) rats or rats made glucoprivic with 2-deoxy-D-glucose (2DG, 200 mg/kg, i.p.) following either vehicle treatment, systemic administration of naltrexone or intracerebroventricular administration of either naltrexone, the mu opioid antagonist, beta-funaltrexamine (B-FNA), the mu1 opioid antagonist, naloxonazine, the kappa opioid antagonist, nor-binaltorphamine (Nor-BNI), the delta opioid antagonist, naltrindole or the delta1 opioid antagonist, DALCE. Systemic administration of naltrexone (0.5-5 mg/kg significantly reduced carbohydrate, fat and total intake in deprived rats, and carbohydrate, fat, protein and total intake in glucoprivic rats. Central administration of naltrexone (5-50 micrograms) significantly reduced fat and total intake in both deprived and glucoprivic rats. B-FNA (5-20 micrograms) significantly reduced carbohydrate, fat and total intake in both deprived and glucoprivic rats Naloxonazine (10-100 micrograms) significantly reduced carbohydrate, fat and total intake in deprived rats, but failed to alter 2DC intake. Nor-BNI (5-20 micrograms) significantly reduced fat and total intake in glucoprivic rats, but failed to alter deprivation intake. Neither naltrindole (20 micrograms) nor DALCE (40 micrograms altered intake in deprived or glucoprivic rats. Carbohydrate or fat preference in deprived rats significantly increased the amount of explained variance in the inhibitory actions of central naltrexone, B-FNA and naloxonazine upon deprivation-induced intake. Carbohydrate or fat preference in glucoprivic rats significantly increased the amount of explained variance in the inhibitory action of systemic and central naltrexone, B-FNA, naloxonazine and Nor-BN upon 2-DG hyperphagia. These data are discussed in terms of the contentions that opioids either selectively alter fat intake pe se or selectively alter the preferred macronutrient.
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PMID:Selective alterations in macronutrient intake of food-deprived or glucoprivic rats by centrally-administered opioid receptor subtype antagonists in rats. 782 Jun 18

Ventricular microinjection studies found that whereas mu (beta-funaltrexamine, B-FNA), mu1 (naloxonazine) and kappa (nor-binaltorphamine, Nor-BNI) opioid receptor antagonists, but not delta antagonists, reduce deprivation-induced intake, kappa and mu, but not mu1 or delta antagonists reduce both 2-deoxy-D-glucose (2DG) hyperphagia and sucrose intake. Since opioid agonists stimulate spontaneous food intake in the accumbens, the present study examined whether administration of either naltrexone, B-FNA or Nor-BNI in the accumbens altered intake under deprivation (24 h), glucoprivic (2DG: 500 mg/kg, i.p.) or palatable sucrose (10%) conditions. Naloxonazine's effects in the accumbens were also evaluated for deprivation-induced intake. Deprivation-induced intake was significantly decreased over 4 h by naltrexone (5-20 micrograms, 44%), B-FNA (1-4 micrograms, 55%) and Nor-BNI (4 micrograms, 31%) but not naloxonazine (10 micrograms) in the accumbens. 2DG hyperphagia was significantly decreased by naltrexone (10-20 microgram, 79%), B-FNA (1-4 micrograms, 100%) and NOR-BNI (104 micrograms, 75%) in the accumbens. Sucrose intake was significantly decreased by naltrexone (50 micrograms, 27%) and B-FNA (1-4 micrograms, 37%), but not NOR-BNI in the accumbens. These data suggest that mu receptors, and particularly the mu2 binding site in the accumbens are responsible for the opioid modulation of these forms of intake in this nucleus, and that this control may be acting upon the amount of intake per se.
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PMID:General, mu and kappa opioid antagonists in the nucleus accumbens alter food intake under deprivation, glucoprivic and palatable conditions. 862 11