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)

In mice, both apomorphine and pilocarpine either potentiated a hypothermic effect of a high dose of morphine or reversed a hyperthermic effect of a low dose of morphine to a hypothermic effect. Haloperidol paritally blocked the hypothermic effect but not the hyperthermic effect of morphine. Scopolamine partially blocked the hyperthermic but not the hypothermic effect of morphine. Bilateral lesions of the caudate nuclei produced no changes in sensitivity to either the acute hyperthermic or hypothermic effect of morphine but did selectively facilitate the developement of tolerance to morphine-induced hypothermia. The results suggest that morphine's temperature effects are determined by the interaction of several mechanisms and that the caudate nucleus may have a specific role in drug tolerance.
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PMID:Hyperthermic and hypothermic effects of morphine in mice: interactions with apomorphine and pilocarpine and changes in sensitivity after caudate nucleus lesions. 114 21

Systemic administration of 4-Aminopyridine at a dose of 4 mg/kg (4-AP) induces hypothermia in mice. Scopolamine (ED50 = 0.26 mg/kg) and two tricyclic antidepressants, desipramine (ED50 = 1.82 mg/kg) and IM/P/3/4 (ED50 = 8.95 mg/kg) completely antagonize 4-AP-induced hypothermia, whereas minaprine (0.1-0.25 mg/kg), a non-tricyclic antidepressant, reverts only 45% of the maximal effect of 4-AP. Oxotremorine at a dose of 0.05 mg/kg (OXO) induces a hypothermic effect comparable to that of 4-AP. Scopolamine (ED50 = 0.011 mg/kg) completely reverts OXO-induced hypothermia whereas desipramine and IM/P/3/4 never produce more than 60% of antagonism over a wide range of doses. Minaprine does not affect OXO-induced hypothermia. These results suggest that the interaction of antidepressants with cholinergic function occurs mainly at the pre-synaptic level.
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PMID:Interaction of antidepressants with 4-aminopyridine. 163 18

Lithium (Li) has been previously reported to increase acetylcholine turnover and release in rat brain and to potentiate the neurotoxicity of cholinergic agents. We studied the effect of chronic Li administration, alone and in combination with the muscarinic antagonist, scopolamine, on two cholinergically-mediated responses and on muscarinic cholinergic receptor (MCR) binding in rat brain. Administered separately, Li and scopolamine enhanced the cataleptic and hypothermic responses to pilocarpine; combined administration resulted in an additive effect on both these measures. [3H]Quinuclidinyl benzilate ([3H]QNB) binding was increased by Li in the corpus striatum but not in the cortex, hippocampus and hypothalamus. Scopolamine increased [3H]QNB binding in the striatum, cortex and hippocampus; Li and scopolamine effects on striatal MCR were not additive. Contrary to a previous report, antagonist-induced MCR supersensitivity was not prevented by concurrent Li administration in any of the brain areas studied. The additive effect of Li and scopolamine on pilocarpine-induced catalepsy and a trend in this direction for pilocarpine-induced hypothermia suggest that the actions of the two agents to enhance cholinergically mediated responses may be achieved by different mechanisms. Supersensitive responses following scopolamine may be attributed to antagonist-induced up-regulation of postsynaptic muscarinic receptors as demonstrated in the binding studies. The effects of Li to enhance cholinergically-mediated catalepsy and hypothermia are interpreted as extending previous reports that Li stimulates brain cholinergic function by a presynaptic increase in acetylcholine turnover and release.
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PMID:Effect of chronic lithium on cholinergically mediated responses and [3H]QNB binding in rat brain. 404 71

1. In unanaesthetized rats, a dose of 50 mug of hemicholinium-3 injected into the cerebral ventricles produced a prolonged hypothermia which was unaffected by the simultaneous administration of choline. This suggests that it was not due to inhibition of acetylcholine synthesis.2. An intraperitoneal injection of 50 mug of hemicholinium-3 also produced hypothermia which, however, was blocked by choline which suggests that it is due to inhibition of acetylcholine synthesis.3. Hyoscine and hexamethonium did not block the hypothermia produced by intraventricular hemicholinium-3, but some antagonism was obtained with phentolamine, imipramine and amphetamine.4. When hemicholinium-3 was administered intraventricularly to rats pretreated with desmethylimipramine, a lethal hyperthermia developed.5. It is concluded that no central cholinergic mechanism is involved in the hypothermia of the rat resulting from an intraventricular injection of hemicholinium-3.
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PMID:Hypothermia following intraventricular injection of hemicholinium-3 in rats. 576 28

Scopolamine was either continuously infused or injected once daily into C3H mice. Chronic infusion resulted in mice that were supersensitive to the hypothermia and tremor produced by the muscarinic agonist, oxotremorine. Chronic scopolamine infusion did not alter brain acetylcholinesterase (AChE) or choline acetyltransferase (ChAT) activities but it did produce an increase in brain muscarinic receptors, as measured by quinuclidinyl benzilate (QNB) binding. The maximal increase in QNB binding was seen at the 0.2 mg/kg/hr dose. Further increase in dose resulted in a return to control QNB binding in all brain regions studied except cortex. These animals were still supersensitive to oxotremorine, suggesting a dissociation between receptor number and response to agonist. Animals injected once daily for 10 days with 5 mg/kg exhibited an increase in QNB binding while no increase was seen at 20 mg/kg/day. Chronic oxotremorine infusion resulted in tolerance to the hypothermia-producing effects of oxotremorine. This was accompanied by a decrease in brain QNB binding. Coinfusion of scopolamine with oxotremorine blocked both the tolerance development and receptor changes. These experiments demonstrate that chronic scopolamine treatment can elicit an increase in brain muscarinic receptors which is accompanied by supersensitivity to agonists. However, this effect is not clearly dose related, and a strict relationship between receptor number and agonist response does not exist.
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PMID:Chronic scopolamine treatment and brain cholinergic function. 673 17

We examined the effects of p.o. administered 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8- yl)-1-propanone fumarate (TAK-147), a novel AChE inhibitor, on impaired learning and memory in animal models. At 1 to 3 mg/kg, TAK-147 ameliorated the passive avoidance deficit induced by diazepam. TAK-147 did not affect delayed-matching-to-position (DMTP) performance of normal rats at doses of 1 to 30 mg/kg assessed by using a three-lever operant chamber, but 9-amino-tetrahydroacridine disrupted the DMTP response at 5 to 20 mg/kg. Scopolamine (0.02-0.1 mg/kg s.c.) impaired DMTP performance, whereas methylscopolamine did not affect the DMTP task. TAK-147 ameliorated the impairment of DMTP performance induced by scopolamine without affecting the general behavior of the rats; however, 9-amino-tetrahydroacridine produced no significant amelioration of the impairment. The intraventricular injection of AF64A disrupted differential-reinforcement-of-low-rate 10-sec performance in rats, as demonstrated by marked decreases in reinforcement rate and response efficiency. TAK-147 slightly increased the reinforcement rate in AF64A-treated rats at a low dose of 1 mg/kg, but the effect was not significant statistically. TAK-147 had no significant effect on the duration of immobility in rats in a forced swimming test at doses of 2 to 10 mg/kg. 9-Amino-tetrahydroacridine prolonged the duration of immobility at 5 to 20 mg/kg. Furthermore, TAK-147 reversed reserpine-induced hypothermia and ptosis in mice at doses of 3 to 10 mg/kg, a result that implies an antidepressant-like action. These results indicate that TAK-147 ameliorates learning and memory impairment in animal models without affecting the general behavior or causing behavioral depression and suggest that TAK-147 may be useful for the treatment of Alzheimer's disease.
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PMID:Effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1 -H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, on impaired learning and memory in animal models. 866 90

Both oxotremorine and physostigmine both in doses ranging from 25 to 100 micrograms/kg produced dose-dependent attenuation of withdrawal jumping and potentiation of 'wet dog' shakes, burrowing, hypothermia and body weight loss precipitated by naloxone (1 mg/kg, i.p.) in morphine-dependent mice. On the other hand, atropine sulphate (2-20 mg/kg) dose-dependently attenuated all naloxone precipitated withdrawal symptoms except withdrawal hypothermia which was further potentiated. However, the peripherally acting derivative atropine methyl nitrate (2-10 mg/kg) also attenuated all naloxone-induced withdrawal symptoms except jumping, which was not significantly modified. Hyoscine (0.2-20 mg/kg) exhibited a biphasic effect on withdrawal jumping. Withdrawal jumping was potentiated by low and attenuated by high doses of hyoscine. Withdrawal body weight loss was dose-dependently attenuated but 'wet dog' shakes, burrowing and hypothermia were markedly potentiated by hyoscine. Our results suggest that a combination of central muscarinic activation and peripheral muscarinic blockade can partially ameliorate precipitated morphine withdrawal. Differences observed between atropine and hyoscine with regard to their modifying effects on withdrawal symptoms may be explained on the basis that the drugs may be acting on the different subpopulations of the muscarinic receptor or through non-cholinergic systems.
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PMID:The role of cholinergic systems in the expression of morphine withdrawal. 882 52

The effects of temperature and scopolamine on dizocilpine maleate-induced neuronal necrosis in the rat cingulate/retrosplenial cortex, entorhinal/olfactory cortices and the dentate gyrus were studied. Mild, protracted hypothermia (48 h at a brain temperature of 34 degrees C), induced by a servo-controlled "exposure technique" in the awake female rat, significantly reduced dizocilpine maleate (5.0 mg/kg, i.p.)-induced neuronal death in the cingulate/retrosplenial and entorhinal/olfactory cortices seven days following drug administration. Scopolamine (0.25 mg/kg, i.p.), putatively neuroprotective [Olney J. W. et al. (1991) Science 254, 1515-1518], did not reduce injury in the cingulate/retrosplenial cortex of female rats following one injection, but did following two and three doses. Scopolamine had no significant effect in the other brain regions. A temperature elevation of only 1 degree C above baseline for 48 h in awake female rats increased dizocilpine maleate-induced damage. Finally, the sex differences in N-methyl-D-aspartate antagonist toxicity were replicated and extended to other structures, and found not to be due to temperature differences. Our data show that dizocilpine maleate neurotoxicity is temperature sensitive. Scopolamine treatment needed to be prolonged in order to reduce injury, and even then was only efficacious in one of three brain regions. The results underscore the importance of using neuronal necrosis in several brain regions as the endpoint and for the use of prolonged therapeutic interventions. Furthermore, given the potential hypothermic action of other putative neuroprotective drugs, a mechanistic re-evaluation of N-methyl-D-aspartate antagonist-induced injury is needed, with precise brain temperature measurement.
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PMID:The effects of temperature and scopolamine on N-methyl-D-aspartate antagonist-induced neuronal necrosis in the rat. 1018 36

Organophosphate pesticides such as chlorpyrifos reduce core temperature (Tc) in laboratory rodents. The mechanism(s) responsible for the chlorpyrifos-induced hypothermia are not well known. This study assessed the role of a key effector for thermoregulation in the rat, vasomotor control of heat loss from the tail, and its possible cholinergic control during chlorpyrifos-induced hypothermia. Tc and motor activity were monitored by telemetry in female Long-Evans rats maintained at an ambient temperature (Ta) of 25 degrees. Tail skin temperature (Tsk(t)) was measured hourly. Rats were dosed with chlorpyrifos (0 or 25 mg/kg orally). Two hr later the rats were dosed with saline or scopolamine (1.0 mg/kg intraperitoneally). Two hr after chlorpyrifos treatment there was a marked elevation in Tsk(t)) concomitant with a 0.5 degrees reduction in Tc. Scopolamine administered to control rats led to a marked elevation in Tc with little change in Tsk(t). Rats treated with chlorpyrifos and administered scopolamine underwent a marked vasoconstriction and elevation in Tc. Vasodilation of the tail is an important thermoeffector to reduce Tc during the acute stages of chlorpyrifos exposure. The blockade of the response by scopolamine suggests that the hypothermic and vasodilatory response to chlorpyrifos is mediated via a cholinergic muscarinic pathway in the CNS.
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PMID:Chlorpyrifos-induced hypothermia and vasodilation in the tail of the rat: blockade by scopolamine. 1098 9

This study presents a comparison between two inhibitors of acetylcholinesterase, tacrine and E2020 (Donepezil), the 5-HT(3) receptor antagonist ondansetron, and the H(3) receptor antagonist thioperamide, in models of cholinergic function and cognition in male, Lister hooded rats. The cognitive tests used were an operant VI20 task, the delayed match to position task (short-term memory) and the 5-choice serial reaction time task (attention). Scopolamine (SCOP) (0.075mg/kg s.c.) was utilised in both the short-term memory and attention tasks to impair performance. Both tacrine (1-30mg/kg) and E2020 (1-10mg/kg) similarly produced overt cholinomimetic signs of likely central origin (hypothermia, tremor), although tacrine produced more profound peripheral cholinomimetic signs (miosis, secretory signs) than E2020. Tacrine (30mg/kg) and E2020 (10mg/kg) reduced the number of reinforcements gained in the VI20 schedule. Similarly, both drugs attenuated the SCOP-impairment models in the short-term memory and attention tasks (1-3mg/kg). Ondansetron (10ng/kg-1mg/kg) and thioperamide (0.2-10mg/kg) failed to elicit overt cholinomimetic signs or influence the number of food reinforcements gained in the VI20 schedule. Neither ondansetron nor thioperamide attenuated the SCOP-induced impairment in either cognitive task. From the present studies, both E2020 and tacrine showed a similar behavioural profile in the models used, although E2020 was about three times more potent. Furthermore, E2020 but not tacrine appeared to show some discrimination in eliciting central and peripheral cholinomimetic signs. The failure of ondansetron and thioperamide to reverse a SCOP-induced deficit in these models is discussed.
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PMID:Effects of anticholinesterase drugs tacrine and E2020, the 5-HT(3) antagonist ondansetron, and the H(3) antagonist thioperamide, in models of cognition and cholinergic function. 1122 48


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