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

Melatonin (10 and 20 mg/kg) potentiated pentobarbitone (45 mg/kg) induced hypnosis; it (50 and 100 mg/kg) decreased both total and ambulatory activity; produced (10, 25 and 50 mg/kg) hypothermia and possessed (10-400 mg/kg) significant analgesic property both in tail-flick and acetic acid-induced writhing tests. Melatonin in low dose (10 mg/kg) significantly reduced the forced-swimming induced immobility period per se and also reserpine induced immobility. While the antinociceptive effect of melatonin was sensitive to reversal by naloxone (2 mg/kg), other CNS depressant profile resembled the effects of benzodiazepines.
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PMID:Central nervous system depressant activities of melatonin in rats and mice. 975 58

Hypothermia results in diminished voluntary muscle activity, and is frequently used as a means of providing deep anesthesia to ectotherms and some mammals. In ectotherms, however, it is unclear if hypothermia produces true pain insensation. A needle-probe thermometer was used to demonstrate in frogs (Rana pipiens) that local hypothermia (9 degrees C) could be induced by placement of a tourniqueted leg into ice water (6 degrees C) for 10 min in contrast to the contralateral nontourniqueted leg (21.8 degrees C) kept out of ice water. Analgesia was tested by placement of dilutions of acetic acid on the rear leg. Further tests using groups of 10 frogs demonstrated that frogs with local hypothermia tolerated greater concentrations of acetic acid (mean acetic acid test score = 11) than morphine (10 mg/kg)-treated (9.6) or nontreated (5.8) frogs. Additional studies showed that morphine analgesia was blocked with naloxone doses as low as 0.01 mg/kg and hypothermia-induced analgesia at 10 mg/kg. Naltrexone blocked morphine analgesia at dosages as low as 0.01 mg/kg and hypothermia-induced analgesia at 0.10 mg/kg. In summary, this study demonstrates that hypothermia induces significant analgesia in an amphibian, and that this analgesia is partially blocked by naloxone and naltrexone, suggesting that the effect is mediated at least partially by opioid receptors.
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PMID:Evaluation of hypothermia-induced analgesia and influence of opioid antagonists in leopard frogs (Rana pipiens). 1034 May 22

Matrine and oxymatrine, major components of Sophora flavescens, were confirmed to have a protective effect on restraint and water immersion stress ulcer in mice. Oxymatrine inhibits the formation of some experimental gastric ulcer, pylorus ligation ulcer and indomethacin ulcer, which are considered to relate to acid secretion. Oxymatrine decreases acid secretion in Shay's rats and inhibits gastric motility induced by restraint and water immersion stress when administered intraduodenally. These results suggest that the protective effect of oxymatrine on stress ulcer is possibly due to a decrease of acid secretion and inhibition of gastric motility. In spite of its weak inhibition of gastric acid secretion, intravenous injection of matrine is rather effective for stress ulcer. Matrine exhibits the inhibition of writhing induced by acetic acid, prolongation of sleeping time induced by pentobarbital, hypothermia and inhibition of locomotor activity induced by methamphetamine. Matrine (i.v.) also inhibits gastric motility induced by restraint and water immersion stress. On the other hand, the administration of matrine exhibits clear contraction on the preparation of the fundus strip of rats at high concentration. The contractile response of the fundus strip to matrine is not inhibited by treatment with tetrodotoxin, and is not modified with atropine, while pretreatment of the fundus strip with antihistamine abolished or reduced the contractile response. It can therefore be assumed that the direct action of matrine on the stomach smooth muscle possibly contributes to the mechanism of the matrine induced inhibition of the spontaneous gastric motility and rise in the tone of stomach, and may play an important role in the protection of the restraint and water immersion stress ulcer formetion.
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PMID:[The pharmacological studies on matrine and oxymatrine]. 1108 13

I.v. administration of disodium salt of the ethylenediamine tetra-acetic acid to continuously immersed white rats intensified the rats' amplitude and rate of the respiration movement. I.v. administration of calcium chloride to the cooled rats diminished by 11.3% the respiration movement amplitude and by 20.7%--the muscles electrical activity. The findings confirm important role of the calcium ions in infringement of physiological functions under conditions of hypothermia.
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PMID:[Effect of calcium ion level in blood on physiological functions in rat subjected to immersion hypothermia]. 1157 27

Psychopharmacological properties of crude extract and essential oil of Lippia multiflora (Lm), a verbenacea of african traditional pharmacopea were investigated in rat using classical methods. The extract of Lm is constituted by an infusion of dried leaves. The essential oil is obtained by hydrodistillation of the dried leaves of Lm with a yield of 0.6%. A dilution of 1% is realised with distilled water and the dose of 2 ml/kg of this solution was chosen for this study. The wistar rats of both sexes weighting between 150 and 250 g are used. Animal's behaviour is observed macroscopically for 12 hours. The spontaneous motor activity is appreciated by method of Martin et al. slightly modified. The number of squares jumped by animals in a rectangular cage is determined in ten minutes. The traction test which measures the time necessary for restoration of posterior paws of rat on metallic bar and the duration of pentobarbital sleeping are used for evaluation of muscle relaxant and sedative effects, respectively. The effects of the two preparations of Lm on apomorphin stereotypies and hypothermia are used to investigate the eventual neuroleptic or antidepressant activity. Analgesic property is evaluated by using acetic acid method. The results are expressed as mean +/- SEM. Data are analysed by using the Dunnett's test. A probability level of 0.05 or less was considered to be stalistically significant. The two preparations of Lm at the doses used are well tolerated by rats. No macroscopic difference is observed in behavioural of control and treated groups. Crude extract and essential oil:--does not modify a spontaneous motor activity: control: 45.00 +/- 5.63; crude extract of Lm: 31.00 +/- 5.63; essential oil of Lm: 28.00 +/- 7.62; diazepam 4 mg/kg: 23.80 +/- 5.27 (P < 0.05);--caused an increase of the time necessary for the restoration of paws on the metallic bar in the traction test: control 1.20 +/- 0.25 sec; crude extract of Lm 5.60 +/- 0.57 sec (P < 0.01), essential oil of Lm. 3.60 +/- 0.57 sec (P < 0.01) diazepam 3.60 +/- 0.57 sec (P < 0.01). The differences between the results obtained with crude extract, essential oil and diazepam are significant;--caused a reduction of abdominal cramps induced by acetic acid, control: 26.80 +/- 0.41; crude extract of Lm: 17.00 +/- 1.45 (P < 0.01); essential oil of Lm: 9.20 +/- 1.91 (P < 0.01) and acetylsalicylic acid (Aspegic*) 25 mg/kg 5.40 +/- 1.25 (P < 0.01). The differences is significant between essential oil and crude extract (P < 0.05) but no significant difference is observed between essential oil and acetylsalicylate of lysin. No activity of the two preparations is observed on apomorphin stereotypia and hypothermia comparatively with haloperidol 4 mg/kg and clomipramin 16 mg/kg respectively. Those results confirm the tranquillizer and analgesic activities of Lm and reveal that the crude extract would be more muscle relaxant and the essential oil more analgesic.
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PMID:[Psychopharmacological properties of crude extract and essential oil of Lippia multiflora]. 1168 58

Neurotensin (NT) is a tridecapeptide neurotransmitter in the central nervous system. It has been implicated in the therapeutic effects of neuroleptics. Central activity of NT can only be demonstrated by direct injection into the brain, since it is readily degraded by peptidases in the periphery. We have developed many NT(8-13) analogs that are resistant to peptidase degradation and can cross the blood-brain barrier (BBB). In this study, we report on one of these analogs, NT77L. NT77L induced hypothermia (ED(50)=6.5 mg/kg, i.p.) but induced analgesia only at the highest dose examined (20 mg/kg, i.p.). Like the atypical neuroleptic clozapine, NT77L blocked the climbing behavior in rats induced by the dopamine agonist apomorphine (600 microg/kg) with an ED(50) of 5.6 mg/kg (i.p.), without affecting the licking and the sniffing behaviors. By itself NT77L did not cause catalepsy, but it moderately reversed haloperidol-induced catalepsy with an ED(50) of 6.0 mg/kg (i.p.). Haloperidol alone did not lower body temperature, but it potentiated the body temperature lowering effect of NT77L. In studies using in vivo microdialysis NT77L showed similar effects on dopamine turnover to those of clozapine, and significantly different from those of haloperidol in the striatum. In the prefrontal cortex, NT77L significantly increased serotonergic transmission as evidenced by increased 5-hydroxyindole acetic acid:5-hydroxytryptamine (5-HIAA:5-HT) ratio. Thus, NT77L selectively caused hypothermia, over antinociception, while exhibiting atypical neuroleptic-like effects.
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PMID:Neurotensin analog selective for hypothermia over antinociception and exhibiting atypical neuroleptic-like properties. 1168 57

N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) cyclohexanecarboxamide (Rec 15/3079) was synthesized with the aim of obtaining a novel compound with 5-hydroxytryptamine (5-HT)(1A) antagonistic properties and activity in controlling bladder function at the level of the central nervous system. Rec 15/3079 showed a selective high affinity for the 5-HT(1A) receptor (K(i) = 0.2 nM). At the human recombinant 5-HT(1A) receptor, Rec 15/3079 acted as a competitive, neutral antagonist in that it did not modify basal [(35)S]guanosine-5'-O-(3-thio)triphosphate binding to HeLa cell membranes but shifted the activation isotherm to 5-HT to the right, in a parallel manner, with a pK(b) value of 10.5. Accordingly, Rec 15/3079 (i.v.) potently antagonized 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT)-induced hypothermia in mice (ID(50) = 20 microg/kg) and 8-OH-DPAT-induced forepaw treading in rats (ID(50) = 36 microg/kg). In vitro Rec 15/3079 was poorly active in antagonizing carbachol-induced bladder (pD'(2) = 5.03) and norepinephrine-induced urethral (apparent pK(b) = 6) contractions. However, in anesthetized rats, Rec 15/3079 (10-100 microg/kg i.v.) blocked isovolumic bladder contractions with no effect on their amplitude. In conscious rats and guinea pigs with bladders filled with saline, Rec 15/3079 (300-1000 microg/kg i.v.) increased bladder volume capacity (BVC) without affecting bladder contractility. In conscious rats with bladders filled with dilute acetic acid, Rec 15/3079 (300 microg/kg i.v.) reversed the decrease of BVC induced by the acid. To evaluate apparent selective effect on lower urinary tract reflexes, Rec 15/3079 was tested in experimental models for sedative, analgesic, anxiolytic, and antidepressant activity. Rec 15/3079 showed only a slight decrease in the duration of immobility in the behavioral despair test (antidepressant activity) at 1 mg/kg i.v. No anxiolytic activity was observed at 10 mg/kg i.v. No effect was observed in the hot plate test, but Rec 15/3079 increased tail-flick latencies after 3 to 10 mg/kg i.v. In conclusion, these studies demonstrate that Rec 15/3079 is endowed with favorable effects on bladder function, and it is devoid of unwanted side effects at the level of central nervous system at doses at least 10-fold higher than those active on the bladder.
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PMID:N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) cyclohexanecarboxamide: a novel pre- and postsynaptic 5-hydroxytryptamine(1A) receptor antagonist active on the lower urinary tract. 1171 92

gamma-Hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is proposed to function as a neurotransmitter or neuromodulator. gamma-Hydroxybutyrate and its prodrug, gamma-butyrolactone (GBL), recently received increased public attention as they emerged as popular drugs of abuse. The actions of GHB/GBL are believed to be mediated by GABAB and/or specific GHB receptors, the latter corresponding to high-affinity [3H]GHB-binding sites coupled to G-proteins. To investigate the contribution of GABAB receptors to GHB actions we studied the effects of GHB in GABAB(1)-/- mice, which lack functional GABAB receptors. Autoradiography reveals a similar spatial distribution of [3H]GHB-binding sites in brains of GABAB(1)-/- and wild-type mice. The maximal number of binding sites and the KD values for the putative GHB antagonist [3H]6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene acetic acid (NCS-382) appear unchanged in GABAB(1)-/- compared with wild-type mice, demonstrating that GHB- are distinct from GABAB-binding sites. In the presence of the GABAB receptor positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol GHB induced functional GTPgamma[35S] responses in brain membrane preparations from wild-type but not GABAB(1)-/- mice. The GTPgamma[35S] responses in wild-type mice were blocked by the GABAB antagonist [3-[[1-(S)-(3,4dichlorophenyl)ethyl]amino]-2-(S)-hydroxy-propyl]-cyclohexylmethyl phosphinic acid hydrochloride (CGP54626) but not by NCS-382. Altogether, these findings suggest that the GHB-induced GTPgamma[35S] responses are mediated by GABAB receptors. Following GHB or GBL application, GABAB(1)-/- mice showed neither the hypolocomotion, hypothermia, increase in striatal dopamine synthesis nor electroencephalogram delta-wave induction seen in wild-type mice. It, therefore, appears that all studied GHB effects are GABAB receptor dependent. The molecular nature and the signalling properties of the specific [3H]GHB-binding sites remain elusive.
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PMID:Specific gamma-hydroxybutyrate-binding sites but loss of pharmacological effects of gamma-hydroxybutyrate in GABA(B)(1)-deficient mice. 1465 21

The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of control). Neither MDMA nor MDA alone induced a significant reduction in regional 5-HT or 5-HIAA concentrations following repeated administration. In conclusion, caffeine promotes the acute and long-term toxicity associated with MDMA and MDA. This is a serious drug interaction, which could have important acute and long-term health consequences for recreational drug users.
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PMID:Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love"). 1618 83

Acetate is activated to acetyl-CoA by acetyl-CoA synthetase 2 (AceCS2), a mitochondrial enzyme. Here, we report that the activation of acetate by AceCS2 has a specific and unique role in thermogenesis during fasting. In the skeletal muscle of fasted AceCS2(-/-) mice, ATP levels were reduced by 50% compared to AceCS2(+/+) mice. Fasted AceCS2(-/-) mice were significantly hypothermic and had reduced exercise capacity. Furthermore, when fed a low-carbohydrate diet, 4-week-old weaned AceCS2(-/-) mice also exhibited hypothermia accompanied by sustained hypoglycemia that led to a 50% mortality. Therefore, AceCS2 plays a significant role in acetate oxidation needed to generate ATP and heat. Furthermore, AceCS2(-/-) mice exhibited increased oxygen consumption and reduced weight gain on a low-carbohydrate diet. Our findings demonstrate that activation of acetate by AceCS2 plays a pivotal role in thermogenesis, especially under low-glucose or ketogenic conditions, and is crucially required for survival.
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PMID:Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2. 1918 75


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