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

Recent studies have demonstrated the neuroprotective properties of the novel imidazoquinoline benzodiazepine receptor partial agonist, PNU-101017, in the gerbil forebrain ischemia model. The compound effectively reduces delayed post-ischemic (5 min bilateral carotid occlusion) hippocampal CA1 neuronal degeneration even when its administration is withheld until 4 h after reperfusion and the effect is unrelated to hypothermia. The purpose of the present study was to determine the comparative abilities of PNU-101017 versus the full agonist diazepam to attenuate post-ischemic CA1 damage. Male gerbils were treated either 30 min before ischemia induction or immediately after reperfusion with an initial dose of PNU-101017 (30 mg/kg i.p.) or diazepam (10 mg/kg i.p.) with a second dose being given at 2 h after reperfusion. Possible hypothermic effects of either compound were prevented by external heating. In vehicle (0.05 N HCl)-treated gerbils, the loss of hippocampal CA1 neurons at 5 days was 85%. PNU-101017 pretreatment reduced the loss to 50% (p<0.05 vs. vehicle) whereas pretreatment with diazepam attenuated damage to only 17% (p<0.001 vs. vehicle). Delaying treatment with PNU-101017 until just after reperfusion still resulted in a reduction in CA1 degeneration statistically that was indistinguishable from that seen with pretreatment. In contrast, diazepam post-treatment did not significantly decrease CA1 neuronal loss. These results suggest that a benzodiazepine receptor partial agonist may have greater neuroprotective practicality than a full agonist for the treatment of global cerebral ischemia. The mechanistic basis for this difference may relate to the partially pro-excitatory neuronal response to endogenous GABA before and after neuronal insult.
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PMID:Comparative neuroprotective properties of the benzodiazepine receptor full agonist diazepam and the partial agonist PNU-101017 in the gerbil forebrain ischemia model. 966 60

In order to evaluate the stressing role of swim hypothermia in producing swim stress-induced analgesia (SSIA), we examined whether a mere decrease in the animals' core temperature without swimming would be sufficient to elicit analgesia. The subjects were Swiss-Webster mice selectively bred for 37 and 40 generations for divergent magnitudes of SSIA. High (HA) and low analgesia (LA) mice were exposed for 15 min to temperatures in the range between -5 and +20 degrees C in 79% He/21% O2 (Heliox) atmosphere. The Heliox exposure produced ambient temperature-dependent hypothermia and analgesia, as assessed with a hot-plate test (56 degrees C). The post-Heliox analgesia was of much higher magnitude in HA than in LA mice. The steeper slope of regression of the magnitude of analgesia upon hypothermia in HA mice indicates that these mice are far more sensitive to the analgesic effect of hypothermia than LA mice. Naltrexone HCl (10 mg/kg i.p.) attenuated analgesia in ambient temperature-dependent manner in HA, but not in LA mice. In view of the apparent similarity of Heliox-induced analgesia and SSIA we suggest that hypothermia is a powerful component of swim stress to induce SSIA in the mouse.
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PMID:Analgesia in selectively bred mice exposed to cold in helium/oxygen atmosphere. 1022 87

The reemergence on the debate of the use of marijuana for medicinal purposes has been the impetus for developing an acceptable delivery form of aerosolized cannabinoids. The goals of the present study were to: (1) develop and characterize the physical properties of an aerosolized form of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent present in marijuana; and (2) assess the pharmacological effects of cannabinoid inhalation in mice. A Small Particle Aerosol Generator (SPAG) nebulizer, used to generate the aerosol, had an output of approximately 0.154 mg/l of aerosolized Delta(9)-THC with a 2.0 microm mass median aerodynamic diameter and a 2.2 geometric standard deviation (GSD). Virtually all the particles were less than 5.0 microm in diameter suggesting that they were sufficiently small to penetrate deeply into the lungs. Inhalation exposure to aerosolized Delta(9)-THC in mice elicited antinociceptive effects that were dependent on concentration and exposure time with an estimated Delta(9)-THC dose of 1.8 mg/kg. On the other hand, inhalation exposure to Delta(9)-THC failed to produce two other indices indicative of cannabinoid activity, hypothermia and decreases in spontaneous locomotor activity. The antinociceptive effects occurred within 5 min of exposure and lasted approximately 40 min in duration. The cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR 141716A), but not naloxone, blocked these antinociceptive effects (AD(50)=0.09 mg/kg) indicating a cannabinoid receptor mechanism of action. Similarly, inhalation exposure to a water soluble cannabinoid analog, 3-(5'-cyano-1', 1'dimethylheptyl)-1-(4-N-morpholinobutyrloxy)-Delta(8)-te trahydrocann abinol (O-1057), produced antinociception that was blocked by SR 141716A. These results demonstrate that the development of an aerosolized form of cannabinoids for human medicinal use is feasible.
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PMID:Pharmacological evaluation of aerosolized cannabinoids in mice. 1088 13

Previous studies suggested that peripheral immune mediators may involve intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have therefore investigated a possible role for vagal CCK-A and 5-HT(3) receptors in the febrile response after intraperitoneal human recombinant interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate (100 or 150 microgram/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In other experiments, rats were treated with either antagonists to the 5-HT(3) receptor (ondansetron HCl; 100 microgram/kg) or the CCK-A receptor (L-364,718, 100 or 200 microgram/kg) in combination with LPS or IL-1beta. CCK administration caused a short-lived hypothermia, but interference with the action of endogenous CCK at CCK-A receptors was without effect on IL-1beta- or LPS-induced fever. Neither activation of 5-HT(3) receptors nor blockade of 5-HT(3) receptors affected body temperature or LPS fever. Taken together, our data support the idea that vagal afferents responsive to pyrogenic cytokines may be different from those responsive to CCK or 5-HT.
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PMID:Vagal CCK and 5-HT(3) receptors are unlikely to mediate LPS or IL-1beta-induced fever. 1095 54

We studied the cannabimimetic properties of N-vanillyl-arachidonoyl-amide (arvanil), a potential agonist of cannabinoid CB(1) and capsaicin VR(1) receptors, and an inhibitor of the facilitated transport of the endocannabinoid anandamide. Arvanil and anandamide exhibited similar affinities for the cannabinoid CB(1) receptor, but arvanil was less efficacious in inducing cannabinoid CB(1) receptor-mediated GTPgammaS binding. The K(i) of arvanil for the vanilloid VR(1) receptor was 0.28 microM. Administered i.v. to mice, arvanil was 100 times more potent than anandamide in producing hypothermia, analgesia, catalepsy and inhibiting spontaneous activity. These effects were not attenuated by the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chloro-phenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide.HCl (SR141716A). Arvanil (i.t. administration) induced analgesia in the tail-flick test that was not blocked by either SR141716A or the vanilloid VR(1) antagonist capsazepine. Conversely, capsaicin was less potent as an analgesic (ED(50) 180 ng/mouse, i.t.) and its effects attenuated by capsazepine. The analgesic effect of anandamide (i.t.) was also unaffected by SR141716A but was 750-fold less potent (ED(50) 20.5 microg/mouse) than capsaicin. These data indicate that the neurobehavioral effects exerted by arvanil are not due to activation of cannabinoid CB(1) or vanilloid VR(1) receptors.
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PMID:Neurobehavioral activity in mice of N-vanillyl-arachidonyl-amide. 1104 Mar 43

In the present study, the interaction of nitric oxide synthase (NOS) inhibitors, L-NAME (N(G)-nitro-L-arginine methyl ester HCl) and L-NA (N(omega)-nitro-L-arginine), and its precursor, L-arginine (2-(S)-2-amino-5-[(aminoiminomethyl)amino] pentatonic acid), with theophylline on mouse body temperature was studied. Intraperitoneal (i.p.) injection of different doses of theophylline altered body temperature. Lower doses of theophylline (12.5 and 25 mg/kg) increased, but a higher dose (100 mg/kg) reduced, the animals' body temperature. The combination of L-arginine (20 and 40 mg/kg) with the highest dose of theophylline potentiated the hypothermic effect induced by the latter drug, while L-arginine by itself did not alter body temperature. L-NAME (10-80 mg/kg) or L-NA (10 mg/kg) plus a lower dose of theophylline (12.5 mg/kg) reduced the theophylline-induced hyperthermic response. L-NA (1, 5, and 10 mg/kg) in combination with the high dose of theophylline (100 mg/kg) also induced greater hypothermia. Both L-NAME and L-NA by themselves reduced body temperature. It is concluded that nitric oxide (NO) may be involved in the effects of theophylline on body temperature in mice.
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PMID:Role of nitric oxide in systemic effect of theophylline on mouse body temperature. 1222 30

Swiss-Webster mice selectively bred for high swim stress-induced analgesia (SSIA) were exposed to continuous ambient cold (5 degrees C) for 6 weeks or to daily 3-min swims for 14 consecutive days either in 20 or 32 degrees C water. Thereafter, mice subjected to the particular procedure were injected intraperitoneally with 10 mg/kg of naltrexone HCl and were tested for modification of the opioid and nonopioid component of SSIA. SSIA was reduced following swims at either water temperature and was antagonized by naltrexone to greater extent than in nonswimming mice. Thus, the nonopioid (i.e. naltrexone-resistant) portion of the overall SSIA was significantly reduced, whereas the opioid (naltrexone-sensitive) portion became relatively augmented. In contrast, SSIA differed neither in magnitude nor in sensitivity to naltrexone between cold-acclimated and unacclimated mice. Swim hypothermia as well as the nonopioid component of SSIA were decreased after repeated swimming at 32 and 20 degrees C, but remained unchanged after cold acclimation. This argues for the essential role of an extrathermal, probably emotional in nature, factor not only in the elicitation of nonopioid SSIA, but also in the modulation of thermoregulatory processes during swimming. We suggest that the emergency component of swim stress, together with initial moderate hypothermic challenge, first produces the opioid form of SSIA, and subsequently, as the swim continues, also affects the thermoregulatory processes maintaining thermal homeostasis. This causes further increase in swim hypothermia and raises its stressing property to induce the nonopioid form of SSIA.
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PMID:Effect of cold acclimation and repeated swimming on opioid and nonopioid swim stress-induced analgesia in selectively bred mice. 1267 68

Although it is widely accepted that delta9-tetrahydrocannabinol (delta9-THC) is the primary psychoactive constituent of marijuana, questions persist as to whether other components contribute to marijuana's pharmacological activity. The present experiments assessed the cannabinoid activity of marijuana smoke exposure in mice and tested the hypothesis that delta9-THC mediates these effects through a CB1 receptor mechanism of action. First, the effects of delta9-THC on analgesia, hypothermia, and catalepsy were compared with those of a marijuana extract with equated delta9-THC content after either i.v. administration or inhalation exposure. Second, mice were exposed to smoke of an ethanol-extracted placebo plant material or low-grade marijuana (with minimal delta9-THC but similar levels of other cannabinoids) that were impregnated with varying quantities of delta9-THC. To assess doses, delta9-THC levels in the blood and brains of drug-exposed mice were determined following both i.v. and inhalation routes of administration. Both marijuana and delta9-THC produced comparable levels of antinociception, hypothermia, and catalepsy regardless of the route of administration, and these effects were blocked by pretreatment with the CB1 antagonist SR141716 [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl]. Importantly, the blood and brain levels of delta9-THC were similar in mice exhibiting similar pharmacological effects, regardless of the presence of non-delta9-THC marijuana constituents. The present experiments provide evidence that the acute cannabinoid effects of marijuana smoke exposure on analgesia, hypothermia, and catalepsy in mice result from delta9-THC content acting at CB1 receptors and that the non-delta9-THC constituents of marijuana (at concentrations relevant to those typically consumed) influence these effects only minimally, if at all.
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PMID:Delta9-tetrahydrocannbinol accounts for the antinociceptive, hypothermic, and cataleptic effects of marijuana in mice. 1583 44

The binding of acids and alkalis, formed in tissues by metabolism, along with oxygen and CO(2) transport are recognise as the principal functions of red blood cells (RBCs). Decreases in internal environment pH may result in activation of potential endogenous cytotoxic metabolites, OH and oxidant formation and, as a consequence, result in oxidative damage of cell membrane leading to hemolysis. The characteristics of acid hemolysis in hibernating mammals have been determined in this study. Parameters of HCl-hemolysis, such as the average time for RBC hemolysis and the population distribution of the response, have been investigated. Measurements were performed within 40-5 degrees C temperature range. The resistance of hibernator RBCs to increased acidity, determined according to the acid hemolysis parameters, was found to reflect whether the animal was in the summer active period or in hibernation, with differences also apparent at different points with the hibernation season itself. It was demonstrated that hemolysis parameters of naturally cold-tolerant organisms are altered by decreases in temperature. We discuss a role of cytoskeletal-membrane interactions as a fast-acting switch of the structural and functional state of hibernator RBCs as an adaptation mechanism to acidosis arising from hypothermia and hypermetabolism.
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PMID:Peculiarities of RBCs resistance to acid hemolysis in hibernating mammals. 1851 52

Disturbances in the serotonergic system are implicated in many central nervous system disorders. The serotonin transporter (SERT) regulates the serotonin homeostasis in the synapse. We recently developed a rat which lacks the serotonin transporter (SERT(-/-)). It is likely that adaptive changes take place at the level of pre- and postsynaptic 5-HT receptors. Because autonomic responses are often used to measure 5-HT(1A) receptor function, we analysed these responses by examining the effects of a 5-HT(1A) receptor agonist and antagonist under in vivo conditions in the SERT(-/-) rat. Moreover, we studied the effect of a mild stressor on the body temperature (stress-induced hyperthermia) because of the known involvement of 5-HT(1A) receptors in this phenomenon. Results show that core body temperature did not differ between genotypes under basal, non-stressed conditions. Compared to SERT(+/+) rats, stress-induced hyperthermia was reduced in SERT(-/-) rats. The 5-HT(1A) receptor agonist [R(+)-N-(2[4-(2,3-dihydro-2-2-hydroxy-methyl-1,4-benzodioxin-5-yl)-1-piperazininyl]ethyl)-4-fluorobenzoamide HCl (flesinoxan) reduced stress-induced hyperthermia in both genotypes. The flesinoxan-induced hypothermia in SERT(+/+) rats was blocked by the 5-HT(1A) receptor antagonist [N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexane carboxamide 3HCl (WAY100635). Moreover, WAY100635-induced hyperthermia in SERT(-/-), but not in SERT(+/+) rats. In SERT(-/-) rats, WAY100635 completely blocked the flesinoxan-induced reduction of stress-induced hyperthermia. Interestingly, flesinoxan-induced hypothermia was absent in SERT(-/-) rats. It is concluded that the SERT knockout rat reveals that 5-HT(1A) receptors modulating stress-induced hyperthermia belong to a population of receptors that differs from that involved in hypothermia.
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PMID:Stress-induced hyperthermia and basal body temperature are mediated by different 5-HT(1A) receptor populations: a study in SERT knockout rats. 1860 2


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