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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraperitoneal administration of allylglycine resulted in a hypothermic response in rats. At a dosage of 90 mg/kg, a significant decrease in temperature was noted at 4 and 8 hr after administration, but no significant difference was noted at 12 hr. The same dose administered intraperitoneally to decapitated rats did not result in a hypothermic response, and intraventricular administration resulted in a rapid onset of hypothermia after 1 hr. These findings are indicative of a central site of action for the allylglycine-induced hypothermia. Quantitative assay of hypothalamic monoamines (norepinephrine, serotonin, and dopamine) did not show any significant changes at 4, 8, and 12 hr postadministration when compared to controls. A significant decrease in hypothalamic gamma-aminobutyric acid was noted at each of these time points when compared to controls. These data suggest an important role for gamma-aminobutyric acid in mammalian thermoregulatory control.
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PMID:Hypothermic response following administration of 2-amino-4-pentenoic acid (allylglycine). 115 58

The anticonvulsant, adverse and biochemical effects of the novel antiepileptic drug vigabatrin (gamma-vinyl GABA), which increases GABA (gamma-aminobutyric acid) levels by inhibition of the GABA degrading enzyme GABA aminotransferase, were examined in amygdala-kindled rats after acute and chronic administration. Vigabatrin proved to be a potent anticonvulsant drug at acute doses (100-200 mg/kg), but during chronic administration, the anticonvulsant activity of the treatment was lost already in the second week of treatment. Tolerance also developed to the adverse effects, i.e. hypothermia, sedation and motor impairment. Determination of vigabatrin in plasma indicated that tolerance was not due to declining drug levels. Furthermore, determination of endogenous amino acids in plasma showed that GABA levels were highly elevated throughout the period of treatment, although the extent of GABA accumulation decreased in the second week. After cessation of chronic treatment with vigabatrin, there was no clear indication of withdrawal symptoms, except a prolonged seizure or afterdischarge duration in experiments with 100 mg/kg per day. The data suggest that chronic treatment with vigabatrin may be associated with a loss of anticonvulsant efficacy, at least when the drug is given as monotherapy.
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PMID:Development of tolerance to the anticonvulsant effect of vigabatrin in amygdala-kindled rats. 161 78

Chronic exposure to ethanol is associated with the development of tolerance to the acute effects of ethanol and a withdrawal syndrome characterized by anxiety and seizure susceptibility. In the present study we examined the ability of flumazenil (Ro15-1788), a benzodiazepine receptor antagonist, to reverse neuronal and behavioral manifestations of ethanol tolerance and dependence. A single injection of flumazenil (10 mg/kg, 14 hr before withdrawal) to mice administered a liquid diet containing ethanol for 10 days, reduced seizure severity during withdrawal from ethanol. Acute tolerance to ethanol-induced hypothermia was not sensitive to flumazenil treatment, but tolerance and diazepam-induced cross-tolerance to the ataxic effects of ethanol were reversed by a single injection of flumazenil given 2 to 26 hr before evaluation of tolerance. At a biochemical level, the ability of benzodiazepine inverse agonists (e.g., Ro15-4513) to reduce the activity of gamma-aminobutyric acid (GABA) receptor-operated chloride channels may represent a neuronal manifestation of ethanol dependence (Buck and Harris, 1990). Flumazenil treatment of ethanol-dependent mice 14 hr before isolation of brain membrane vesicles partially reversed the augmentation of Ro15-4513 inhibition of muscimol-stimulated 36Cl- uptake in vitro. These results demonstrate that brief occupation of benzodiazepine receptors by an antagonist may reset the cellular mechanisms responsible for the development of ethanol tolerance and dependence, and support the hypothesis that increased sensitivity to benzodiazepine inverse agonists is involved in the development of ethanol dependence.
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PMID:Reversal of alcohol dependence and tolerance by a single administration of flumazenil. 164 33

1. Amphetamine-induced hypothermia in mice is facilitated by dopaminergic stimulation and 5-hydroxytryptaminergic inhibition. The present study was designed to investigate: (a) the involvement of other neuronal systems, such as the gamma-aminobutyric acid (GABA), the opioid and the cholecystokinin (CCK-8) systems; (b) the possible contribution of hydroxylated metabolites of amphetamine to the hypothermia; (c) the capacity of dopamine itself to induce hypothermia and its mechanisms, in order to clarify the resistance of amphetamine-induced hypothermia to certain neuroleptics. 2. Pretreatment with the GABA antagonists, bicuculline and picrotoxin, did not inhibit amphetamine-induced hypothermia. The GABAB agonist, baclofen (2.5 mg kg-1, i.p.) potentiated this hypothermia, whereas the GABAA agonist, muscimol, did not. gamma-Butyrolactone (GBL) (40 mg kg-1, i.p.) and the neuropeptide CCK-8 (0.04 mg kg-1, i.p.) also induced potentiation. The opioid antagonist, naloxone, was without effect. 3. Dopamine itself (3, 9, 16 and 27 micrograms, i.c.v.) induced less hypothermia than the same doses of amphetamine. Sulpiride did not block dopamine-induced hypothermia, but pimozide (4 mg kg-1, i.p.), cis(z)flupentixol (0.25 mg kg-1, i.p.) and haloperidol (5 micrograms, i.c.v.) did. The direct dopamine receptor agonist, apomorphine, did not alter the hypothermia. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the inhibitor of 5-HT synthesis, p-chlorophenylalanine (PCPA), modified dopamine-induced hypothermia. Fluoxetine, an inhibitor of 5-HT reuptake, had no effect, whereas quipazine (6 mg kg-1, i.p.), a 5-HT agonist, totally prevented the hypothermia. Hypothermia was unaffected by pretreatment with CCK-8. 4. These data indicate that the hypothermia induced by amphetamine involves not only dopaminergic and 5-hydroxytryptaminergic systems which are functionally antagonistic, but is also facilitated by direct or indirect GABA and CCK-8 receptor stimulation. This facilitation could result, in part, from modulation of dopaminergic neurotransmission. This may explain the apparent resistance of amphetamineinduced hypothermia to some neuroleptics, while dopamine-induced hypothermia is not resistant. The possible action of hydroxylated metabolites of amphetamine may also help to explain these differences.
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PMID:Facilitation of amphetamine-induced hypothermia in mice by GABA agonists and CCK-8. 185 28

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose (60 mg/kg intraperitoneally). Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time. Ketamine and hypothermia were without protective effect. Protection from acute radiation-induced mortality by pentobarbital in the rat model is a reproducible phenomenon and is associated with the GABA agonistic activity of the compound. This property of GABA agonists offers the potential for a novel approach to enhancement of the efficacy of radiation therapy in the treatment of brain tumors.
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PMID:Cerebral radioprotection by pentobarbital: dose-response characteristics and association with GABA agonist activity. 215 27

Genetic influences on the interaction between ethanol (ETOH) and gamma-aminobutyric acid (GABA) neurotransmitter systems were evaluated with a survey of responses to coadministration of ETOH and a GABA antagonist, bicuculline, in a battery of inbred mouse strains. The selectively bred ETOH-sensitive Long-Sleep (LS) mice, the relatively ETOH-resistant Short-Sleep (SS) mice, and a genetically heterogeneous stock (GHS) were also evaluated. The effect of bicuculline on ETOH-induced sedation, hypothermia, and blood ethanol content upon recovery from sedation was assessed. Inheritance of these responses was also examined using F1 hybrids. The effect of bicuculline on ETOH-produced narcosis varied widely among stocks and included antagonism, potentiation, and no effect. Changes in ETOH-induced narcosis produced by bicuculline were accompanied by changes in blood ethanol concentrations consistent with an hypothesis of altered central nervous system sensitivity to ETOH. Knowledge of a strain's seizure susceptibility to the GABA antagonist or of its sensitivity to the hypnotic effects of ETOH were of no predictive value in estimating the outcome of coadministration studies, suggesting at least partially separate genetic influences on each phenotype. In cross-breeding studies there was commonly dominance toward a profile of bicuculline antagonism of ETOH narcosis but different patterns of dominance were observed for seizure susceptibility, again indicating separate genetic control. The results suggest considerable complexity of GABAergic involvement in genotype-dependent ETOH sensitivity.
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PMID:Modification of ethanol effects by bicuculline: genotype-dependent responses and inheritance. 250 98

Hibernation was induced in hamsters by placing them in a cold room for an extended period of time, after which the hibernating state was confirmed by marked reductions in heart rate, body temperature, and the respiratory rate. The animals were either frozen intact in liquid nitrogen, or aroused and then frozen when body temperature reached 8, 12, 16, 20, 24 or 32 degrees C. A metabolite profile, including glucose-related metabolites, high-energy phosphates, gamma-aminobutyric acid (GABA) and cyclic nucleotides, was determined for both the cerebral cortex and cerebellum. In general, the metabolite changes in the two regions elicited by hypothermia were alike, although some differences were evident. The brains of hibernators were biochemically characterized by (1) a high concentration of energy reserves including glycogen, glucose, adenosine triphosphate, and P-creatine, (2) significantly elevated levels of lactate and GABA, and (3) near depletion of cyclic guanosine monophosphate with only a moderate depression of cyclic adenosine monophosphate. During arousal, the metabolites were restored to near normal values and there was little or no indication that the brain energy metabolism was compromised by the arousal process. The study provides certain insights into the metabolic adaptation of the brain to prolonged periods of profound hypothermia in a hibernating species.
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PMID:Metabolism in the hamster brain during hibernation and arousal. 274 44

The effects of gamma-aminobutyric acid (GABA) on body temperature of restrained rats has been studied. GABA (250-1000 mg/kg i.p.) caused a dose-dependent fall in BT of restrained rats at an ambient temperature of 18-22 degrees C. The GABA-induced hypothermic response was attenuated by pretreatment with hexamethonium, p-chlorophenylalanine, methysergide, neostigmine and atropine (% MPE values: 27, 35, 51, 64 and 72 respectively). Pretreatment with methysergide and atropine was more potent than hexamethonium and methysergide in inhibiting the GABA-induced hypothermia (% MPE = 68 and 47 respectively). The antagonism by neostigmine of GABA-induced hypothermia was attenuated by pretreatment with hexamethonium (7.5 mg/kg). Yohimbine and chlorimipramine potentiated GABA hypothermia (% MPE = -82 and -8 respectively). The data indicate that GABA-induced hypothermia may be mediated by serotonin and acetylcholine release. Muscarinic receptors may play an important role in the effect of GABA. The results support the hypothesis that the hypothermia induced by GABA is modulated by nicotinic receptors.
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PMID:GABA-induced hypothermia in rats: involvement of serotonergic and cholinergic mechanisms. 294 36

We identified changes in hippocampal afterdischarge activity that follow administration of subcon vulsant doses (one-half the convulsant dose) of analeptic agents with known pharmacological action. Long-Evans rats (N = 104) with chronic bipolar electrodes implanted in the dorsal hippocampus, were injected i.p. with saline, caffeine (75 mg/kg), picrotoxin (2 mg/kg), or pentylenetatrazol (20 mg/kg) in 1 ml/kg volume 15 min before testing. Body temperature was measured at the beginning of the session to determine if significant change was associated with any of the treatments. Beginning at 10 microA, current (2-s train of 50-Hz biphasic pulses) was applied to hippocampal electrodes and intensity was increased in 10-microA steps until the afterdischarge sequence was elicited. Afterdischarge threshold, wet dog shake frequency, and the duration of the primary afterdischarge, the postprimary depression, and the rebound afterdischarge were measured. Caffeine administration produced a dramatic prolongation of the rebound afterdischarge, without affecting the duration of the primary afterdischarge. All other afterdischarge variables were unchanged by the caffeine treatment. Because caffeine blocks adenosine receptors at physiologic concentrations, adenosine action is implicated in the termination of the second, but not the first, spike train. Picrotoxin and pentylenetetrazol had no influence on the EEG, despite evidence of slight (1 degrees C) hypothermia. A decrease in wet dog shake frequency, however, was associated with picrotoxin administration. As picrotoxin and pentylenetetrazol are known gamma-aminobutyric acid (GABA) antagonists, the results suggest that GABA is involved minimally, if at all, in the hippocampal afterdischarge sequence.
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PMID:Differential effects of caffeine, picrotoxin, and pentylenetetrazol on hippocampal afterdischarge activity and wet dog shakes. 356 62

Gamma-aminobutyric acid (GABA) was injected intraperitoneally (i.p.) in conscious restrained rats and the effects on core temperature were observed. GABA (250-1000 mg/kg) produced a dose-dependent decrease in core temperature at an ambient temperature of 22 +/- 1 degree C. GABA-induced hypothermia (1000 mg/kg) was attenuated by pretreatment with reserpine (2 mg/kg, i.p.), p-chloro-phenyl-alanine (300 mg/kg, i.p.), yohimbine (0.25 mg/kg, i.p.) or methysergide (2.5 mg/kg, i.p.). Neither alpha-methyl-p-tyrosine (200 mg/kg, i.p.), nor phenoxybenzamine (5 mg/kg, i.p.), nor pimozide (0.5 mg/kg i.p.) antagonized GABA-induced hypothermia. Pretreatment with either propranolol (10 mg/kg, i.p.) or bicuculline (3 mg/kg, i.p.) potentiated hypothermia induced by GABA. It is concluded that hypothermia produced by i.p. injection of GABA could be due to release of serotonin by activation of bicuculline-insensitive GABA receptors located on central serotonergic neurons.
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PMID:Hypothermic effect of GABA in conscious restrained rats and its modification by monoaminergic blocking drugs. 360 97


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