Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of the GABA(B) receptor antagonist, phaclofen to alter behavioral effects of ethanol was evaluated by loss of righting reflex (sleep time), motor incoordination (bar holding), spontaneous locomotion (open field activity) and hypothermia. Pretreatment with phaclofen significantly decreased the effects of ethanol on motor incoordination, locomotor activity and hypothermia. However, phaclofen had no effect on either pentobarbitalor diazepam-induced motor incoordination. Phaclofen slightly increased the ED50 for loss of the righting reflex but did not alter either the duration of reflex loss produced by ethanol or blood ethanol levels at awakening. Our results suggest phaclofen is rapidly inactivated resulting in difficulty in observing antagonism of long duration ethanol effects. These findings suggest that the GABA(B) system may play a role in mediating several important actions of ethanol.
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PMID:A new alcohol antagonist: phaclofen. 255 16

An imbalance of excitatory and inhibitory amino acid-ergic neurotransmission has been suggested to play a role in the pathogenesis of hepatic encephalopathy. For further evaluation of this hypothesis, several parameters of amino acid-ergic neurotransmission were studied in rats with acute liver failure induced by the administration of 300 mg per kg thioacetamide by gavage on two consecutive days. By appropriate supportive care, hypoglycemia, renal failure and hypothermia were avoided. Rats were monitored clinically and neurologically. Hepatic encephalopathy evolved in four distinct, easily recognizable stages. Light and electron microscopic examination of brains of rats with hepatic encephalopathy revealed only a slight swelling of nuclei of neurons and astrocytes without signs of neuronal degeneration or brain edema. In rats with hepatic encephalopathy, the concentrations of GABA, glutamate and taurine were decreased in the cerebral cortex, the hippocampus and the striatum, whereas those of aspartate and glycine were unchanged or increased. GABAA and benzodiazepine receptors were studied as parameters for the postsynaptic GABAA-benzodiazepine receptor complex, glutamic acid decarboxylase as parameter for presynaptic GABA-ergic neurons and stimulation of benzodiazepine binding by GABA as a parameter for a GABA-mediated postsynaptic event. None of these parameters was different in hepatic encephalopathy as compared to controls. Similarly, Ca++/Cl(-)-dependent and -independent glutamate receptors as parameters for glutamatergic neurons were unchanged in rats with hepatic encephalopathy. Thus, in rats with thioacetamide-induced liver failure and hepatic encephalopathy, changes of the concentrations of neurotransmitter amino acids occur in the brain. Other neurochemical parameters, however, failed to identify alterations of GABA-ergic or glutamatergic neurotransmission in hepatic encephalopathy.
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PMID:Hepatic encephalopathy in thioacetamide-induced acute liver failure in rats: characterization of an improved model and study of amino acid-ergic neurotransmission. 256 68

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and MIF-1 (Pro-Leu-Gly-NH2) can increase GABA-stimulated benzodiazepine binding in brain tissue can block the hypothermia induced by several other compounds. Since benzodiazepines can also cause hypothermia, colonic temperatures were measured in mice after administration of chlordiazepoxide (CDP) and these two brain peptides. In several experiments involving different doses and times of administration of CDP, MIF-1, and Tyr-MIF-1, there were no significant effects of the peptides in altering the reliable decrease in colonic temperature induced by the benzodiazepine. The results indicate that the interaction of Tyr-MIF-1 and MIF-1 with benzodiazepines does not involve thermoregulation.
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PMID:MIF-1 and Tyr-MIF-1 fail to alter benzodiazepine-induced hypothermia. 257 Nov 69

The ability of the putative ethanol antagonist RO 15-4513 to antagonize ethanol - induced hypoactivity, hypothermia and hyperglycemia was investigated in rats. Although RO 15-4513 produced hypoactivity by itself, it attenuated ethanol - induced hypoactivity. This antagonism suggests that ethanol - induced hypoactivity is mediated by the GABA-benzodiazepine receptor complex which is thought to be the site of action of RO 15-4513. In contrast, although RO 15-4513 produced hypothermia by itself, it had no significant effect on ethanol - induced hypothermia. This suggests that the hypothermic effect of ethanol is not mediated by the GABA-benzodiazepine receptor complex. The fact that RO 15-4513, ethanol and the vehicle all produced hyperglycemia suggests a common stress effect and does not permit any firm conclusions to be drawn as to the interaction between ethanol and RO 15-4513 in modulating glycemic responses. These data indicate that the ethanol antagonism of RO 15-4513 is primarily confined to ethanol's behavioural effects and that ethanol's behavioural and physiological effects are mediated by neurochemically distinct mechanisms.
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PMID:The intrinsic and interactive effects of RO 15-4513 and ethanol on locomotor activity, body temperature, and blood glucose concentration. 281 3

GABA, delta-aminovaleric acid (DAVA) and sodium valproate (VPA) decrease core temperature in conscious rats. Bicuculline increases GABA-induced hypothermia, does not modify DAVA (250 mg/kg) and VPA (100 and 400 mg/kg) hypothermia and antagonizes initial hypothermia by DAVA (1000 mg/kg) and VPA (200 mg/kg) and late hypothermia by DAVA (500 mg/kg) and VPA (200 mg/kg). Picrotoxin increases late hypothermia by GABA (250 mg/kg) and VPA (400 mg/kg), but decreases initial hypothermia by VPA (200 mg/kg). Pentylenetetrazol increases variably GABA-induced hypothermia, inhibits early early hypothermia by DAVA and increases hypothermia induced by VPA (400 mg/kg). We conclude that GABA and GABA-agonists (DAVA and VPA) may induce hypothermia partly mediated by activation of bicuculline-insensitive GABA-receptors.
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PMID:Involvement of bicuculline-insensitive receptors in the hypothermic effect of GABA and its agonists. 299 72

Acute exposure of adult male albino rats (110-120 g) to higher environmental temperature (40 +/- 1 degrees C) increased body temperature (BT). This increase of BT was also dependent on the duration of exposure. Treatment with muscimol (1 mg/kg, i.p.), a GABA agonist, produced hypothermia at room temperature (28 +/- 1 degree C) and resistance to increase the body temperature when exposed to higher temperature (40 +/- 1 degree C). Administration of bicuculline (1 mg/kg, i.p.), a GABA antagonist, on the other hand, enhanced BT more than that observed in control (normal) rat exposed to higher temperature (40 +/- 1 degree C), although at room temperature bicuculline treatment did not show any effect on BT. Pretreatment with ethanolamine-O-sulfate (EOS) (2 g/kg, s.c.), a GABA transaminase inhibitor, to rats exposed to higher temperature increased BT as in control (normal) rat. Inhibition of central GAD activity with mercaptopropionic acid (MPA) (70 mg/kg, i.p.) produced resistance to increase BT during its period of action when rats were exposed to higher environmental temperature (28 +/- 1 degree C). These results thus suggest that central inhibitory neuron, GABA, plays a regulatory role in thermoregulation.
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PMID:Involvement of GABA in environmental temperature-induced change in body temperature. 323 43

A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones was prepared and evaluated for potential antidepressant activity. Members of this series were generally prepared by the alkaline ring closures of the corresponding 1-aroylthiosemicarbazides. Several members of this series were potent antagonists of both RO 4-1284-induced hypothermia and reserpine-induced ptosis in mice. In general the more active members of this series were substituted by haloaryl groups at the 5-position of the triazole nucleus and by methyl groups at the 2- and 4-positions. Exchange of the thiocarbonyl group at the 3-position for a carbonyl group resulted in the complete loss of activity. Biochemical evaluation of the more active members of this series indicated that the aforementioned activities were not a consequence of either norepinephrine (NE) uptake or monoamine oxidase inhibition. In an attempt to determine a mechanism of action, one member of this series, compound 22, was selected for further evaluation in an electrophysiological model where it was found to reduce norepinephrine function in the cerebellum as measured by the NE augmentation of GABA inhibition of Purkinje neurons.
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PMID:2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents. 337 95

The imidazobenzodiazepine, Ro15-4513, which is a partial inverse agonist at brain benzodiazepine receptors, reversed the incoordinating effect of ethanol in mice, as measured on an accelerating Rotarod. This effect was blocked by benzodiazepine receptor antagonists. In contrast, Ro15-4513 had no effect on ethanol-induced hypothermia in mice. However, Ro15-4513 reversed the hypothermic effect of pentobarbital, and, at a higher dose, also reversed the incoordinating effect of pentobarbital in mice. The data support the hypothesis that certain of the pharmacological effects of ethanol are mediated by actions at the GABA-benzodiazepine receptor-coupled chloride channel.
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PMID:Effect of an imidazobenzodiazepine, Ro15-4513, on the incoordination and hypothermia produced by ethanol and pentobarbital. 360 Jan 96

Electrophysiological aspects of thiamine depletion in the rat induced by dietary deficiency are described. Behavioral changes as well as qualitative and quantitative alterations in the sensitivity of cerebellar Purkinje cells to iontophoretically-applied 5-hydroxytryptamine (5-HT) were observed. Thiamine-deficient rats were characterized essentially by ataxia, piloerection, paresis, apparent weakness, and hypothermia after 4-6 weeks on a thiamine-free diet. Basal Purkinje cell firing frequency was unaffected by thiamine deficiency. The response of Purkinje cells to iontophoretically-applied 5-HT was solely inhibitory in deficient rats. In control rats, however, responses to 5-HT were excitatory, biphasic, or inhibitory. Neurons in the thiamine-deficient animals were more sensitive to the inhibitory effects of 5-HT, as demonstrated by a significant parallel shift to the left of the dose-response curve. Durations of 5-HT effects were similar in both groups. Dose-response relationships for GABA-induced inhibition of Purkinje cell firing from thiamine deficient and control rats did not differ from one another. These data demonstrate a relatively selective effect of thiamine depletion on cerebellar serotonergic neurotransmission assessed electrophysiologically. We believe there is up-regulation of 5-HT receptors on Purkinje cells caused by thiamine deficiency-induced impairment of indoleamine input to the cerebellum from raphe and related nuclei.
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PMID:Enhanced sensitivity of cerebellar Purkinje cells to iontophoretically-applied serotonin in thiamine deficiency. 398 3

Cranio-cerebral hypothermia (temperature of the body 32-30 degrees C, of the brain 29-27 degrees C) was studied for its effect on the reuptake of neuromediators (3H-noradrenaline and [14C]GABA) by the cortex and hypothalamus synaptosomes of the rat brain. It was found that the reuptake of [3H]noradrenaline by the cortex synaptosomes under narcosis and cranio-cerebral hypothermia was inhibited much stronger than that by the hypothalamus synaptosomes. At the same time GABA-ergic synapses of the cortex and hypothalamus were not sensitive to narcosis. Cranio-cerebral hypothermia essentially inhibited the reuptake of [14C] GABA by synaptosomes and hypothalamus.
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PMID:[Effect of hypothermia on reuptake of neuromediators by synaptosomes]. 400 72


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