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 hyperphagia and obesity induced by ventromedial hypothalamic (VMH) electrolytic lesions in female rats were associated with a 70-94% decrease in the level of beta-endorphin (beta-E) in the hypothalamus and other regions of brain, but not in the pituitary. Dynorphin (Dyn) and methionine-enkephalin (ME) levels were also decreased. Rats with VMH lesions were less sensitive to the inhibitory effect of naloxone on their food-intake. Mice injected with gold thioglucose (GTG) also showed a decrease in the hypothalamic content of beta-E and Dyn and exhibited 30% less analgesia compared to control mice after cold swim stress.
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PMID:Effect of electrolytic and chemical ventromedial hypothalamic lesions on food intake, body weight, analgesia and the CNS opioid peptides in rats and mice. 289 79

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

2-Deoxy-D-glucose (2DG) analgesia, mediated in part by endogenous opiate and hypothalamo-hypophysial systems is presumably activated by its stress-related properties. Recently 2DG hyperphagia, but not 2DG hyperglycemia was reduced by central pretreatment with the pancreatic beta-cell toxin, alloxan; this deficit was eliminated by co-administration of 3M D-glucose. The present experiment examined whether intracerebroventricular pretreatment with alloxan (40 or 200 micrograms) altered 2DG analgesia (400 or 700 mg/kg, IP) on the tail-flick and jump tests, and whether 3M D-glucose co-administration ameliorated any deficits. Both alloxan doses significantly reduced 2DG analgesia (400 mg/kg) on both tests. 2DG analgesia (700 mg/kg) was significantly reduced by both alloxan doses on the jump test, but only by the higher alloxan pretreatment on the tail-flick test. 3M D-glucose co-administration ameliorated alloxan-induced analgesic deficits more effectively at the lower 2DG dose. Neither alloxan nor alloxan/3M D-glucose treatments altered basal thresholds. These data pertain both to alloxan's effects upon coding of 2DG effects as stressful, and to the role of diabetes and/or central glucoreceptors in analgesic processes.
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PMID:Intracerebroventricular alloxan reduces 2-deoxy-D-glucose analgesia. 339 8

The present study assessed in rats the effects of muscarinic receptor antagonism upon analgesia induced by cold-water swims (CWS: 2 degrees C for 3.5 min) and 2-deoxy-D-glucose (2DG: 600 mg/kg). First, CWS analgesia was significantly reduced 30 min after the swim by scopolamine (0.01 and 0.1 mg/kg) and methylscopolamine (10 mg/kg) pretreatment, and was eliminated 60 min after the swim by scopolamine (0.01-10 mg/kg) and methylscopolamine (1,10 mg/kg) pretreatment. In contrast, scopolamine potentiated CWS hypothermia. Second, while scopolamine (1 mg/kg) and methylscopolamine (1,10 mg/kg) pretreatment prolonged 2DG analgesia, both antagonists dose-dependently reduced 2DG hyperphagia. Third, the changes in analgesic and hypothermic stress responses were not due to baseline shifts in jump thresholds or body temperatures. However the dose-dependent reductions by scopolamine and methylscopolamine in baseline food intake and 2DG hyperphagia were significantly correlated. Fourth, the dose-dependent reduction by scopolamine and methylscopolamine of pilocarpine analgesia differed in pattern from the other analgesic effects, suggesting heterogeneity in muscarinic receptor modulation of different analgesic responses.
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PMID:Effects of muscarinic receptor antagonism upon two forms of stress-induced analgesia. 374 24

Among the compromised physiological responses affected by aging is an impaired response to glucose. Since administration of 2-deoxy-D-glucose (2DG) produces both analgesic and hyperphagic responses in young adult rats, the present study examined whether systematic variations in these responses occurred as a function of age. Separate cohorts of 4, 9, 14, 19 and 24 month old female rats received ascending doses of 2DG (0, 50, 250, 450, 650 mg/kg) with tail-flick latencies and jump thresholds assessed 30, 60 and 120 min later. Then the same rats received 2DG injections (0, 650, 1200 mg/kg) and food intake was assessed 5 hr later. Significant decreases in 2DG analgesia were observed on the tail-flick test as a function of age with the maximal decrease observed at the highest 2DG dose. Significant decreases in 2DG analgesia were generally observed on the jump test as a function of age, although this effect was not as robust as that observed on the tail-flick test. Finally, significant and systematic decreases in 2DG hyperphagia were observed as a function of age following both the 650 mg/kg and the 1200 mg/kg doses. The observed decrements in the analgesic and hyperphagic responses to 2DG as a function of age appear to represent an orderly alteration in responses to glucoprivation through adulthood.
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PMID:Age-related decrements in the analgesic and hyperphagic responses to 2-deoxy-D-glucose. 386 4

Injection of 2-deoxy-D-glucose (2DG) elicits both analgesic and hyperphagic responses in rats. While pituitary dysfunction, decreased dopamine availability, or neonatal monosodium glutamate treatment decreases 2DG hyperphagia, they increase 2DG analgesia. In contrast, 2-DG analgesia alone is decreased by repeated 2-DG injections, while 2-DG hyperphagia alone is decreased following naloxone pretreatment. The present four experiments examined further mechanisms subserving these two induced responses. In the first experiment, rats were deprived of food for 6 h following 2-DG (600 mg/kg). While 2-DG hyperphagia persisted in the absence of glucoprivation, 2-DG analgesia failed to occur after this delay. In the second experiment, acute exposure to inescapable foot shock (4 mA, 0.5 s/5 s for 1 h) preceded administration of 2-DG (600 mg/kg). While 2-DG hyperphagia was eliminated by this procedure, 2-DG analgesia was significantly potentiated. In the third experiment, repeated morphine (10 mg/kg) injections over 14 days eliminated 2-DG analgesia on the fifteenth day, but failed to affect 2-DG hyperphagia. In the fourth experiment, lesions placed in either the lateral hypothalamus or zona incerta decreased 2-DG hyperphagia, but failed to affect 2-DG analgesia. These results are discussed in terms of common and dissociative mechanisms mediating both responses.
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PMID:Dissociation of analgesic and hyperphagic responses following 2-deoxy-D-glucose. 658 11

Neonatal administration of monosodium glutamate (MSG) produces in rats neurotoxic degeneration of the circumventricular system, including the medial-basal hypothalamus, depleting several neuropeptides and neurotransmitters in this area. In addition, a number of behavioral and neuroendocrine responses are impaired, including a significant decrease in the analgesic response to cold-water swims (CWS). The present study examined whether the alterations in the analgesic responses following CWS and 2-deoxy-D-glucose (2-DG) induced by neonatal MSG treatment were due either to direct alterations in a pain-inhibitory system, or alternatively, to alterations in a system that processes the stressful consequences or properties of a stimulus. To accomplish this, the analgesic, hypothermic, and locomotor responses following CWS and the analgesic, hyperphagic, and locomotor responses following 2-DG were assessed in rats treated neonatally (days 2, 4, 6, 8, and 10) with either MSG or a vehicle solution. MSG-treated rats displayed significant reductions in both their analgesic and hypothermic responses following CWS, suggesting that MSG treatment impairs an animal's ability to process sufficiently the stimulus properties of the swim as stressful. While MSG treatment potentiated 2-DG analgesia, it reduced 2-DG hyperphagia, suggesting that MSG treatment also impairs coping responses to glucoprivation. These data indicate the importance of the circumventricular system in the coding of stimuli as potential stressors and in the subsequent activation of requisite systems necessary to provide a sustained, coordinated, and synchronous coping response.
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PMID:Impairments in analgesic, hypothermic, and glucoprivic stress responses following neonatal monosodium glutamate. 673 8

The glucose analogue, 2-deoxy-D-glucose (2-DG) elicits hyperphagic and analgesic responses in rats. The former response appears to be mediated by central processes since overeating is elicited following intraventricular administration of 2-DG at low (3.5 and 5.0 mg/kg) doses. The present study examined whether flinch-jump threshold would increase 30, 90 and 180 min following intraventricular injections of 2-DG at low (3.5, 5.0 and 10.0 mg/kg) doses and compared these effects with systemically-applied 2-DG doses of 350 and 500 mg/kg. Intraventricular 2-DG administration increased jump thresholds for up to 180 min across all test doses. Flinch thresholds were also increased, but in a manner dissociated from jump thresholds. Animals with cannulae located near, but not in the lateral ventricle, displayed delayed analgesic effects. The magnitude of intraventricular 2-DG analgesia was not at potent as the 100-fold higher systemic injections. It appears that central mechanisms mediated intraventricular 2-DG analgesia at the low dose range since higher, systemic 2-DG doses have previously failed to increase flinch-jump thresholds.
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PMID:Analgesia following intraventricular administration of 2-deoxy-D-glucose. 723 79

Pharmacological studies suggest that diabetes produces changes in the brain opioid system, affecting several behavioral functions including analgesia, feeding and self-stimulation. Previous investigations of opioid receptor binding have failed to explain the unusual opioid pharmacology of the diabetic animal. In the present study, the effects of streptozotocin-induced diabetes on levels of three immunoreactive (ir)-prodynorphin-derived peptides, ir-dynorphin A1-17 (A1-17), ir-dynorphin A1-8 (A1-8) and ir-dynorphin B1-13 (B1-13), were determined in eleven brain regions known to be involved in appetite, taste and reward. Diabetes was found to increase levels of A1-17 in the ventromedial and dorsomedial hypothalamic nuclei (+60% and +25%, respectively) and levels of A1-8 in the dorsomedial and lateral hypothalamus (+45% and +35%, respectively). The possible significance of these results is discussed in relation to (i) diabetic hyperphagia, (ii) medial hypothalamic transduction of circulating insulin levels, and (iii) the potentiation of reward by metabolic need states.
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PMID:Effects of streptozotocin-induced diabetes on prodynorphin-derived peptides in rat brain regions. 758 38

MOR-1 encodes a mu receptor. In an effort to establish the relationship of this cloned opioid receptor with ingestive behavior and analgesia in rats, the present study examined the actions of four antisense oligodeoxynucleotides aimed at exons 1 (AS1), 2 (AS2), 3 (AS3) and 4 (AS4) of the MOR-1 clone, as well as a mismatch antisense sequence (MS1). Rats were administered intracerebroventricular injections (10 micrograms/2 microliters) of each of the oligodeoxynucleotides on days 1, 3 and 5. Body weight and spontaneous food and water intake were monitored daily. In addition, 2-deoxy-D-glucose (2DG)-induced hyperphagia, central Angiotensin II (ANG-II) induced hyperdipsia and central morphine analgesia were examined 24 h following the last antisense injection. AS1, AS2, AS3 and AS4 each significantly reduced body weight (7-17 g), food intake (8-13 g) and water intake (11-23 ml), while the vehicle or MS1 conditions significantly increased weight (9-20 g) and produced smaller reductions (2-4 g) in food intake. None of the AS probes altered the magnitude of either 2DG-induced hyperphagia or ANG-II-induced hyperdipsia. Central morphine analgesia was reduced by pretreatment with AS1 and AS4, but not AS2, AS3 or MS1. The sensitivity of general feeding to all four exons suggest that the receptor responsible for this action is encoded by the MOR-1 clone. The differences between feeding and morphine analgesia raise the possibility that these two actions are mediated through different mu receptor subtypes. Our results also demonstrate the viability of the in vivo antisense technique in modulating opioid-mediated ingestive responses.
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PMID:Antisense oligodeoxynucleotides against the MOR-1 clone alter weight and ingestive responses in rats. 878 66


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