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

The responses of catecholamine systems in long sleep (LS) and short sleep (SS) mice to alpha-methyl-p-tyrosine (AMPT) have been examined. Marked differences were found between LS and SS mice in the dose necessary for maximal brain catecholamine depletion and in the time-course of the catecholamine depletion. Brain catecholamines in the LS mice were depleted by lower doses of AMPT and the levels remained depressed for longer periods of time in this line of mice. These differences may be explained only partially by an increased susceptibility of the LS mice to the hypothermia and toxic effects caused by AMPT administration, as they persist with non-toxic AMPT dosage regimens and under conditions where the degree of hypothermia is comparable in both lines of mice. In addition, there were no differences between the Ki values for the effect of AMPT on the tyrosine hydroxylase from striata of these mouse lines. The primary cause of the heightened response to AMPT in LS mice would appear to be pharmacokinetic in nature, as brain and plasma peak levels of AMPT in LS mice were greater and the levels remained higher for a longer time. The depletion of brain tyrosine by AMPT combined with the lower affinity of the LS striatal tyrosine hydroxylase for the substrate tyrosine may also contribute to the heightened response in LS mice.
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PMID:Alpha-methyl-para-tyrosine effects in mice selectively bred for differences in sensitivity to ethanol. 286 56

Long-sleep (LS) and short-sleep (SS) lines of mice were selectively bred for differences in CNS sensitivity to ethanol with LS mice exhibiting much greater sensitivity to hypnotic doses of ethanol (4.0-4.5 g/kg) than SS mice. The influence of peripheral and central catecholamine neuronal systems on ethanol sensitivity (sleep time) in LS and SS mice was examined following administration of reserpine, alpha-methyl-p-tyrosine and 6-hydroxydopamine. Ten days after a single dose of reserpine, tyrosine hydroxylase activity was increased in the brain and adrenal gland of LS mice but only in the brain of SS mice relative to untreated mice. Brain catecholamine levels in the reserpine-treated mice were 25-50% lower in both LS and SS mice compared to levels in untreated mice. These changes were associated with a 41% reduction in LS sleep time, but a 90% increase in SS sleep time. SS mice were also more susceptible to the lethal effects of reserpine. The increased mortality of SS mice may relate to a greater degree of reserpine-induced hypothermia and a slower rate of recovery of brain catecholamine levels. Neonatal LS and SS mice treated with 6-hydroxydopamine exhibited increased levels of catecholamines in the locus ceruleus, decreased levels in the cerebellum and unchanged levels in the hypothalamus at 60 days of age. These changes were associated with a modest decrease (10%) in LS sleep time and a marked increase (200%) in SS sleep time. alpha-Methyl-p-tyrosine decreased brain catecholamine levels of both lines by 30-50% while LS sleep times were unchanged and SS sleep times were increased by 45%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Further studies on the neurochemical mechanisms mediating differences in ethanol sensitivity in LS and SS mice. 289 2

The present study examined the effects of exposure of rats to elevated environmental levels of CO2 on norepinephrine metabolism in the hypothalamus and other regions of the brain. In confirmation of previous findings by others CO2 at 10 or 15% was found to elevate both dopa accumulation after dopa decarboxylase inhibition and norepinephrine utilization after tyrosine hydroxylase inhibition. These effects however were found to be transient occurring only during the first 30 min of 2.5 h exposure. In this regard CO2 differs from another form of stress, restraint which produces a sustained 2.5 h increase of dopa accumulation and NE accumulation. Restraint was also more effective than CO2 in depleting endogenous stores of hypothalamic NE. The factor responsible for the adaptation of the catecholamine response to CO2 was not identified although it was shown not to be hypothermia and it was reversed by a 2 h CO2-free recovery period.
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PMID:Rapid adaptation of the stimulatory effect of CO2 on brain norepinephrine metabolism. 642 Jul 12

Arousal at birth is likely to be accompanied by changes in gene expression patterns in the brain. We analyzed the expression levels of genes that may be involved in neonatal adaptation. We have also tried to dissect the effect of hypoxia and hypothermia, two components that may play a role in gene expression at birth. Therefore, we analyzed the expression patterns of the c-fos, tyrosine hydroxylase, enkephalin, preprotachykinin-A, and neuropeptide Y genes in various brain regions of rat pups at various time points after cesarean section under normal conditions and after exposure to hypoxia and hypothermia. We found that c-fos RNA was up-regulated transiently after birth in neocortex, midbrain, and pons-medulla with a maximum of 30 min after cesarean section, and that this transient increase was not further augmented by hypoxia and hypothermia. The expression patterns of the other genes were not significantly altered, with the exception of a very slight increase in tyrosine hydroxylase RNA levels. We discuss tentative mechanisms for the transient increase in c-fos expression and the possible involvement of catecholamines in this process.
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PMID:Expression of c-fos, tyrosine hydroxylase, and neuropeptide mRNA in the rat brain around birth: effects of hypoxia and hypothermia. 770 Jul 28

The role of catecholamine neuronal systems in mediating the analeptic and thermogenic effects of thyrotropin-releasing hormone (TRH) was examined in long-sleep (LS) and short-sleep (SS) mice. TRH [0.1 to 40 micrograms, intracerebroventricularly (icv)] was associated with a reduction in the sleep times of LS mice, but no dose of TRH had any effect on sleep times of SS mice. However, TRH (20 micrograms, icv) produced a 1.0 degree to 1.5 degrees C attenuation of the ethanol-induced hypothermia in both LS and SS mice. TRH did not change the rate of ethanol elimination in either line of mice, suggesting that the reduction in LS sleep times and attenuation of LS and SS hypothermia were due to decreased CNS ethanol sensitivity rather than an increase in the rate of ethanol metabolism. TRH (20 micrograms, icv) given alone produced an activation of central and peripheral catecholamine systems in LS, but not SS mice, as reflected by an increase in the in vivo tyrosine hydroxylase (TH) activity in the brain and adrenal gland. TRH, given with ethanol, prevented or attenuated ethanol-induced decreases in the brain and adrenal gland in vivo TH activity in LS mice but not SS mice. Thus, there was an association between the ability of TRH to produce an activation of catecholamine neuronal systems (increased rate of catecholamine biosynthesis) and the analeptic action of TRH to reduce the CNS depressant effects of ethanol (decreased sleep times).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of thyrotropin-releasing hormone and catecholaminergic interactions on CNS ethanol sensitivity. 809 74

The postnatal development of certain neurochemical correlates of CNS ethanol sensitivity was examined in the long-sleep (LS) and short-sleep (SS) mice. The differences in sensitivity to the motor-incoordinating and hypothermic effects of ethanol emerged during the second and third weeks of life. Prior studies have shown the sleep time differences between LS and SS mice became significant at 8-10 days of age whereas the present results established that the differences in ethanol-induced hypothermia became prominent at 12-16 days of age. Previous results from our laboratory suggested that the greater CNS ethanol behavioral sensitivity (sleep time and hypothermia) of LS mice is related to the greater ethanol-induced depression of brain monoamine synthesis in the LS line. The timing of the developmental changes in neurochemical ethanol sensitivity in LS and SS mice was found to parallel that found in the development of behavioral ethanol sensitivity as follows. Ethanol-induced decreases in in vivo tyrosine hydroxylase activity in the cerebellum, hypothalamus, and brain stem did not differ between LS and SS mice at postnatal day 8, but became substantially greater in LS mice between postnatal days 8 and 12, coincident with the appearance of the greater sleep times of LS mice. Likewise, ethanol-induced decreases in in vivo tryptophan hydroxylase activity in the dorsal raphe and hypothalamus, which were similar in LS and SS mice at postnatal days 8 and 12, became significantly greater in LS mice by postnatal day 16, the age at which their increased sensitivity to ethanol-induced hypothermia appeared.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of neurochemical and behavioral sensitivity to ethanol in long-sleep and short-sleep mice. 851 37

Amphetamines (AMPs) can cause long-term depletions in striatal dopamine (DA) and serotonin (5-HT), and these decrements are often accepted as prima facie evidence of AMP-induced damage to the dopaminergic and serotonergic projections to striatum. Rarely are indices linked to neural damage used to evaluate the neurotoxicity of the AMPs. Here, we determined the potential neurotoxic effects of two substituted AMPs, d-methylenedioxymethamphetamine (d-MDMA) and d-fenfluramine (d-FEN) in group-housed female C57BL6/J mice. Astrogliosis, assessed by quantification of glial fibrillary acidic protein (GFAP), was the main indicator of d-MDMA-induced neural damage. Assays of tyrosine hydroxylase (TH), DA, and 5-HT were used to determine effects on DA and 5-HT systems. Since AMPs are noted for both their stimulatory and hyperthermia-inducing properties, activity, as well as core temperature, was monitored in several experiments. To extend the generality of our findings, these same end points were examined in singly housed female C57bL6/J mice and in group-housed male C57BL6/J or female B6C3F1 mice after treatment with d-MDMA. Mice received either d-MDMA (20 mg/kg) (singly housed mice received dosages of 20, 30, or 40 mg/kg) or d-FEN (25 mg/kg) every 2 h for a total of four sc injections. d-MDMA caused hyperthermia, whereas d-FEN induced hypothermia. d-MDMA cause a large (300%) increase in striatal GFAP that resolved by 3 wk and a 50-75% decrease in TH and DA that was still apparent at 3 wk, d-FEN did not affect any parameters in striatum. d-MDMA is a striatal dopaminergic neurotoxicant in both male and female C57BL6/mice, as evidenced by astrogliosis and depletions of DA in this area in both sexes. The greater lethality to males suggests they may be more sensitive, at least to the general toxicity of d-MDMA, that females. d-MDMA (20 mg/kg) induced the same degree of damage whether mice were housed singly or in groups. Higher dosages in singly housed mice induced greater lethality, but not greater neurotoxicity. d-MDMA was also effective in inducing striatal damage in mice of the B6C3F1 strain. Significant increases in activity were induced by d-MDMA, and these increases were not blocked by pretreatment with MK-801, despite the profound lowering of body temperature induced by this combination. A lowering of body temperature, whether by a 15 degree C ambient temperature (approx 2 degree drop), pretreatment with MK-801 (1.0 mg/kg prior to the first and third d-MDMA injections; approx 5-6 degrees C drop) or restraint (approx 5-6 degrees C drop) was effective in blocking the neurotoxicity of d-MDMA in both C57BL6/J and B6C3F1. The stimulatory effects of d-MDMA appeared to have little impact on the neurotoxicity induced by d-MDMA or the protection conferred by MK-801. These data suggest that in the mouse, the neurotoxic effects of d-MDMA, and most likly other AMPs, are linked to an effect on body temperature.
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PMID:The role of temperature, stress, and other factors in the neurotoxicity of the substituted amphetamines 3,4-methylenedioxymethamphetamine and fenfluramine. 856 61

Substantial evidence suggests that stress can alter the general toxicological properties of the substituted amphetamines (AMPs) as well as their psychostimulant properties. Research concerning the interactions between stress and the neurotoxicity associated with the AMPs is, however, limited. Our previous work demonstrated that a variety of AMPs, including d-METH, d-MDA, d-MDMA but not d-FEN are able to damage dopaminergic elements of the striatum as shown by decreases in dopamine and tyrosine hydroxylase. The neurotoxic capabilities of these AMPs appear linked to their hyperpyrexic actions as diverse manipulations able to block AMP-induced hyperthermia are also neuroprotective. Surprising, since stress usually potentiates the actions of the AMPs, it is our finding that restraint, a commonly used stressor, is protective against the injurious actions of all neurotoxic AMPs evaluated to date. In the mouse restraint acts to elevate blood levels of corticosterone (CORT) by activating the hypothalamic-pituitary-adrenal (HPA) axis as well as inducing a profound hypothermia. The role CORT may play in the neuroprotective actions of restraint, if any, is unknown. Here, data is presented showing the impact of several HPA axis manipulations, including restraint, supplementation with CORT in the drinking water and removal of CORT by adrenalectomy (ADX) on the striatal dopaminergic neurotoxicity of d-AMP. As strain is known to be a powerful determinant of the actions of stress an essential element of these experiments was the evaluation of both an inbred, C57BL/6J and outbred, CD-1, mouse strain. Exposure to d-AMP caused hyperthermia and substantial striatal dopaminergic neurotoxicity in both strains suggesting that an elevation in body temperature is as important a component of the neurotoxicity of d-AMP, as it is of the other neurotoxic AMPs. Restraint was equally effective in both strains and completely blocked the hyperthermia and striatal neurotoxicity induced by d-AMP. CORT supplementation, evaluated in only the C57BL/6J mouse at dosages not capable of involuting either the thymus or the spleen, did not alter d-AMP-induced neurotoxicity. Although the immune system organs of the two strains responded differentially to the removal of CORT, ADX provided equivalent partial protection against the loss of dopaminergic elements in striatum for both strains. Adrenal status clearly affects d-AMP neurotoxicity but the interaction is complex. Future work should examine the roles of the cortical and medullary components of the adrenal gland in the neuroprotective actions of ADX. A precise assessment of the role of circulating CORT In the neurotoxicity of the AMPs will require additional work in which a wider range of CORT dosages, including those capable of involuting thymus and spleen, are evaluated.
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PMID:Neurotoxicity of d-amphetamine in the C57BL/6J and CD-1 mouse. Interactions with stress and the adrenal system. 895 30

(R)-apomorphine is a non-selective dopamine (DA) agonist which is used in the treatment of Parkinson's disease. In addition to symptomatic effects, apomorphine exerts a neuroprotective activity in specific experimental models. For instance, apomorphine prevents experimental parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine does not seem to be related to its dopamine (DA) agonist properties, instead it appears to be grounded on the antioxidant and the free radical scavenging effects of the compound. In this study, we sought to determine whether apomorphine protects against methamphetamine toxicity. We found that apomorphine (1; 5 and 10 mg/kg) dose-dependently protects against methamphetamine- (5 mg/kg X3, 2 h apart) induced striatal DA loss and reduction of tyrosine hydroxylase (TH) activity in the rat striatum. These protective effects are neither due to a decrease in the amount of striatal methamphetamine nor to hypothermia as indicated by measurement of striatal methamphetamine and body temperature at different time intervals after drug administration. The effects of apomorphine were neither opposite to, nor reversed by the DA antagonist haloperidol despite no decrease in body temperature was observed when apomorphine was given in combination with haloperidol. The present data are in line with recent studies suggesting a DA receptor-independent neuroprotective effect of apomorphine on DA neurons and call for further studies aimed at evaluating potential neuroprotective effects of apomorphine in Parkinson's disease.
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PMID:Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage. 1129 46

Body temperature profiles observed during methamphetamine (METH) exposure are known to affect dopamine and tyrosine hydroxylase (TH) levels in the striatum of mice; hyperthermia potentiates depletion while hypothermia is protective against depletions. In the current study, the doses of METH were sufficiently great that significant dopamine and TH depletions occurred even though hypothermia occurred. Four doses, administered at 2 h intervals, of 15 mg/kg (4x15 mg/kg) D-METH significantly decreased TH and dopamine levels to 50% of control in mice becoming hypothermic during dosing in a 13 degrees C environment. Phenobarbital or dizocilpine during METH exposure blocked the depletions while diazepam did not. Phenobarbital and dizocilpine did not block depletions by altering the hypothermic profiles from that observed during METH only exposure. Here we show that phenobarbital and dizocilpine can block measures of METH neurotoxicity by non-thermoregulatory mechanisms.
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PMID:Phenobarbital and dizocilpine can block methamphetamine-induced neurotoxicity in mice by mechanisms that are independent of thermoregulation. 1168 78


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