naloxone and Hyperphagia

Topics: Analgesia; Animals; Cold Temperature; Deoxyglucose; Endorphins; Hyperphagia; Hypophysectomy; Hypothalamus; Morphine; Naloxone; Pain; Physical Exertion; Rats; Rats, Brattleboro; Sensory Thresholds; Stress, Physiological; Vasopressins

There is evidence that endogenous opiates are involved in the control of feeding in experimental animals. Several types of experimental obesity are associated with increased opiate production and/or increased numbers and sensitivity of opiate receptors. Research with experimental animals suggests that nutrients, particularly sugar, have an effect on feeding behavior that is mediated by opiates. For instance, the obesity-producing effect of a palatable diet in rodents is blocked by opiate antagonists. Stress induced feeding in rodents leads to preferential sucrose ingestion and is blocked by opiate antagonists and beta-endorphin. The effect of nutrients on the endogenous opiate system of humans is less clear. Clinical experience suggest that carbohydrates (sugar in particular) play a role in binge eating and obesity. Many binge eaters preferentially eat sweets during a binge. Many obese individuals consume more than half of their total daily calories as carbohydrates. Sweet snacking is a frequent behavior at times of stress. Recent evidence suggests that sugar can lead to increased beta-endorphin production in obese subjects.

Topics: Animals; beta-Endorphin; Diet; Endorphins; Feeding and Eating Disorders; Feeding Behavior; Glucose; Humans; Hyperphagia; Male; Naloxone; Narcotics; Obesity; Time Factors

Recent reports have indicated that the incidence of anorexia nervosa and bulimia has increased over the last several years. Both of these syndromes present serious treatment challenges to clinicians and in an effort to deal more effectively with these disorders several pharmacological interventions have been attempted. This article reviews the range of pharmacological interventions used with anorexia nervosa and bulimia patients. The purpose of the review is to present our current knowledge regarding the efficacy of these medications and to offer methodological recommendations that will enhance future research efforts.

Topics: Adrenocorticotropic Hormone; Anorexia Nervosa; Antidepressive Agents, Tricyclic; Chlorpromazine; Cyproheptadine; Dopamine; Feeding and Eating Disorders; Female; Humans; Hyperphagia; Levodopa; Lithium; Lithium Carbonate; Male; Naloxone; Phenytoin; Pimozide; Serotonin; Zinc

Benzodiazepines reliably produce overconsumption of food and fluids. Opiate antagonists, naloxone and naltrexone, block the benzodiazepine-induced hyperphagia and hyperdipsia at low doses. Hence, activation of endogenous opioid mechanisms may be closely involved in the benzodiazepine facilitatory effects on ingestional behavior. Evidence is reviewed that opiate antagonists diminish feeding and drinking responses, and may enhance satiety processes in feeding and drinking, in addition to selectively diminishing the palatability of attractive foods and fluids. It is proposed that a single mechanism of action of the opiate antagonists would be sufficient to account for both effects on feeding and drinking. Biochemical data confirm that acute benzodiazepine treatment in vivo is associated with a naloxone-reversible release of striatal enkephalin. It is possible therefore that there is a close association between the behavioral and biochemical data, which both show that acute benzodiazepine effects are reversed by opiate antagonists. The implied relationship between benzodiazepine and endogenous opioid mechanisms may be relevant to the question of concurrent opiate-benzodiazepine abuse.

Topics: Animals; Benzodiazepines; Corpus Striatum; Drinking Behavior; Enkephalins; Feeding Behavior; Food Deprivation; Humans; Hyperphagia; Motor Activity; Naloxone; Naltrexone; Narcotic Antagonists; Reward; Thirst

Topics: Adrenal Glands; Animals; Body Weight; Central Nervous System; Diet; Digestive System Physiological Phenomena; Eating; Energy Intake; Energy Metabolism; Feeding Behavior; Humans; Hyperphagia; Hypothalamus; Models, Biological; Morphine; Naloxone; Obesity; Satiety Response

A regular daily meal regimen, as opposed to ad libitum consumption, enforces eating at a predefined time and within a short timeframe. Hence, it is important to study food intake regulation in animal feeding models that somewhat reflect this pattern. We investigated the effect of scheduled feeding on the intake of a palatable, high-sugar diet in rats and attempted to define central mechanisms - especially those related to opioid signaling--responsible for overeating sweet foods under such conditions. We found that scheduled access to food, even as challenging as 20 min per day, does not prevent overconsumption of a high-sucrose diet compared to a standard one. An opioid receptor antagonist, naloxone, at 0.3-1 mg/kg b. wt., decreased the intake of the sweet diet, whereas higher doses were required to reduce bland food consumption. Real-time PCR analysis revealed that expression of hypothalamic and brainstem genes encoding opioid peptides and receptors did not differ in sucrose versus regular diet-fed rats, which suggests that scheduled intake of sweet food produces only a transient change in the opioid tone. Intake of sugar was also associated with upregulation of orexin and oxytocin genes in the hypothalamus and NPY in the brainstem. We conclude that scheduled consumption of sugar diets is associated with activity of a complex network of neuroregulators involving opioids, orexin, oxytocin and NPY.

Topics: Animals; Appetite Regulation; Dietary Sucrose; Eating; Food Preferences; Hyperphagia; Intracellular Signaling Peptides and Proteins; Naloxone; Neurons; Neuropeptide Y; Neuropeptides; Neurotransmitter Agents; Opioid Peptides; Orexins; Oxytocin; Rats; Rats, Sprague-Dawley

Proopiomelanocortin (POMC) neurons in the hypothalamus are direct targets of the adipostatic hormone leptin and contribute to energy homeostasis by integrating peripheral and central information. The melanocortin and beta-endorphin neuropeptides are processed from POMC and putatively coreleased at axon terminals. Melanocortins have been shown by a combination of pharmacological and genetic methods to have inhibitory effects on appetite and body weight. In contrast, pharmacological studies have generally indicated that opioids stimulate food intake. Here we report that male mice engineered to selectively lack beta-endorphin, but that retained normal melanocortin signaling, were hyperphagic and obese. Furthermore, beta-endorphin mutant and wild-type mice had identical orexigenic responses to exogenous opioids and identical anorectic responses to the nonselective opioid antagonist naloxone, implicating an alternative endogenous opioid tone to beta-endorphin that physiologically stimulates feeding. These genetic data indicate that beta-endorphin is required for normal regulation of feeding, but, in contrast to earlier reports suggesting opposing actions of beta-endorphin and melanocortins on appetite, our results suggest a more complementary interaction between the endogenously released POMC-derived peptides in the regulation of energy homeostasis.

Topics: Animals; beta-Endorphin; Eating; Energy Metabolism; Glucose; Homeostasis; Hyperinsulinism; Hyperphagia; Leptin; Male; Mice; Mice, Knockout; Naloxone; Narcotic Antagonists; Neuropeptide Y; Obesity; Reference Values

Neurons that synthesize the morphine modulatory peptide neuropeptide FF (NPFF; Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) densely innervate the parabrachial nucleus (PBN), an area implicated in regulating food intake. We analyzed opioid-related actions of NPFF in feeding in adult male Sprague-Dawley rats. Unilateral infusion of 2 nmol/0.5 microl of the mu-opioid receptor agonist [d-Ala2,NMe-Phe4,glycinol5]enkephalin (DAMGO) into the lateral PBN increased 4-h food intake from 0.7 +/- 0.1 to 3.3 +/- 0.3 g. NPFF (1.25-5.0 nmol) prevented this hyperphagic mu-opioidergic action. In rats fed after 4-h deprivation (baseline = 12.3 +/- 0.3 g/2 h), 5 nmol of NPFF did not alter and larger doses (10 and 20 nmol) actually increased food intake (+36, 54%). Twenty nanomoles also elevated intake of freely feeding rats (from 0.7 +/- 0.1 to 5.1 +/- 1.0 g/4 h). The opioid receptor blocker naloxone (10 nmol) antagonized this increase. These data reveal both pro- and anti-opioid actions of NPFF in the PBN to modulate feeding. The mechanisms for the opposite actions of low and high concentrations of this neuropeptide in parabrachial regulation of food intake remain to be determined.

Topics: Analgesics, Opioid; Animals; Dose-Response Relationship, Drug; Drinking; Eating; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Feeding Behavior; Hyperphagia; Immunohistochemistry; Male; Naloxone; Narcotic Antagonists; Oligopeptides; Pons; Rats; Rats, Sprague-Dawley

The pontine parabrachial nucleus (PBN) has been implicated in regulating ingestion and contains opioids that promote feeding elsewhere in the brain. We tested the actions of the selective mu-opioid receptor (mu-OR) agonist [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) in the PBN on feeding in male rats with free access to food. Infusing DAMGO (0.5-4.0 nmol/0.5 microl) into the lateral parabrachial region (LPBN) increased food intake. The hyperphagic effect was anatomically specific to infusions within the LPBN, dose and time related, and selective for ingestion of chow compared with (nonnutritive) kaolin. The nonselective opioid antagonist naloxone (0.1-10.0 nmol intra-PBN) antagonized DAMGO-induced feeding, with complete blockade by 1.0 nmol and no effect on baseline. The highly selective mu-opioid antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 1.0 nmol) also prevented this action of DAMGO, but the kappa-antagonist nor-binaltorphimine did not. Naloxone and CTAP (10.0 nmol) decreased intake during scheduled feeding. Thus stimulating mu-ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate mu-ORs in the LPBN in the normal regulation of food intake.

Topics: Analgesics, Opioid; Animals; Eating; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Feeding Behavior; Food Deprivation; Hyperphagia; Male; Naloxone; Narcotic Antagonists; Peptide Fragments; Peptides; Pons; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Somatostatin

Feeding induced in rats by cerebroventricular (i.c.v.) injection of orphanin FQ was potently and dose-dependently reversed by peripheral injection of either the opioid antagonist naloxone or the cannabinoid CB(1) receptor antagonist SR 141716[N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophelyl)-4-methyl-3-pyrazole-carboxamine]. The combination of these two agents inhibited food intake in a manner suggestive of additivity or supra-additivity.

Topics: Animals; Dose-Response Relationship, Drug; Drug Synergism; Eating; Female; Hyperphagia; Male; Naloxone; Narcotic Antagonists; Nociceptin; Opioid Peptides; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Drug; Rimonabant

Delta and kappa opioid receptors have been differentiated into further subtypes based upon both biochemical and pharmacological analgesic assays. Whereas hyperphagia elicited by the kappa1 receptor agonist, U50488H is blocked by general and kappa1 opioid antagonists, hyperphagia elicited by the kappa3 receptor agonist, naloxone benzoylhydrazone (NalBzOH) is blocked by general, but not kappa1 opioid antagonists. The first study assessed the opioid antagonist profile of hyperphagia elicited by centrally administered delta1 ([D-Pen2, D-Pen5]-enkephalin, DPDPE: 5-50 microg) and delta2 ([D-Ala2, Glu4]-Deltorphin, Delt II: 5-50 microg) agonists following central pretreatment with general (naltrexone), delta1 ([D-Ala2, Leu5, Cys6]-enkephalin, DALCE) and delta2 (naltrindole isothiocyanate, NTII) opioid antagonists. It is also important to determine whether selective opioid receptor subtype agonists are capable of altering intake in ingestive situations other than spontaneous feeding. The second study examined whether centrally administered delta1, delta2, kappa1 or kappa3 agonists altered the pattern and magnitude of hyperphagia elicited by 2-deoxy-D-glucose (2DG: 50-400 mg/kg, IP). DPDPE-induced hyperphagia was significantly reduced by naltrexone and NTII, but not DALCE. Delt II-induced hyperphagia was significantly reduced by DALCE and NTII, but not naltrexone. Pairing Delt II (5 microg) with low (100-200 mg/kg) 2DG doses significantly enhanced intake, producing a leftward (3-fold) shift in 2DG's hyperphagic dose-response curve. In contrast, DPDPE failed to alter 2DG-induced hyperphagia, and kappa1 and kappa3 opioid agonists each produced small, but significant increases in 2DG-induced hyperphagia. The antagonist data suggest the possibility of physiological and pharmacological interactions between delta receptor subtypes in mediating food intake, and it would appear that delta2 opioid receptors exert facilitatory effects upon glucoprivic hyperphagia.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Cerebral Ventricles; Deoxyglucose; Dose-Response Relationship, Drug; Drug Synergism; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Hyperphagia; Infusions, Parenteral; Male; Naloxone; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Regression Analysis

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and MIF-1 (Pro-Leu-Gly-NH2) act as opiate antagonists in various behavioral systems including ingestion. Central injection of peptide YY (PYY) elicits a powerful feeding response in satiated rats, and the opioid antagonist naloxone decreases eating in a variety of conditions including PYY-stimulated eating. Therefore, the aim of this study was to examine the effects of Tyr-MIF-1 and MIF-1 as opiate antagonists on a naloxone-sensitive PYY model of hyperphagia. Naloxone at doses of 1.0 and 10.0 mg/kg, SC, decreased hyperphagia induced by 2.4 micrograms PYY injected in the PVN. MIF-1 and Tyr-MIF-1 had no effect on PYY-induced eating at doses comparable to naloxone (0.1 to 10.0 mg/kg, IP). These results suggest that in this model of eating behavior, Tyr-MIF-1 and MIF-1 do not act as opiate antagonists.

Topics: Animals; Behavior, Animal; Feeding Behavior; Hyperphagia; Male; MSH Release-Inhibiting Hormone; Naloxone; Peptide YY; Peptides; Rats; Rats, Sprague-Dawley

Diazepam and pentobarbital administered intravenously increased food intake in a dose-dependent manner in nondeprived rats. Low doses of naloxone inhibited diazepam-induced feeding, but did not inhibit pentobarbital-induced feeding. On the other hand, picrotoxin inhibited feeding induced by both drugs. These findings suggest that diazepam-induced hyperphagia is related to endogenous opioid mechanisms, but pentobarbital-induced hyperphagia is not. Hyperphagia induced by both drugs may be related to GABAergic neurons.

Topics: Animals; Diazepam; Dose-Response Relationship, Drug; Feeding Behavior; Hyperphagia; Male; Naloxone; Pentobarbital; Picrotoxin; Rats; Rats, Inbred Strains