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)

L-Methionine-D,L-sulfoximine (MSO), intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.) (third ventricle) injected at a convulsant dose, induced a centrally mediated body hypothermia in the restrained rat maintained at an ambient temperature of 23 degrees C. Pretreatment with (+/-)-pindolol (1.5-3 mg/kg s.c.) significantly attenuated MSO-induced hypothermia, but at a dose of 6 mg/kg s.c. hypothermia developed without any modification of its characteristics. Pretreatment with (-)-propranolol (16-25 mg/kg i.p.) potentiated MSO-induced hypothermia, but pretreatment of MSO-treated rats with ketanserin (0.7-4 mg/kg i.p.) did not significantly modify hypothermia. Selective antagonists for beta-adrenoceptors were used and their effects on MSO-induced hypothermia were compared with those of pindolol and propranolol. Pretreatment with betaxolol (1.5-4 mg/kg s.c.) did not modify the hypothermia following administration of MSO, but potentiation of hypothermia was recorded in rats pretreated with ICI 118,551 (2.26 mg/kg i.p.) then i.p. injected with MSO. These findings favour a control exerted by 5-HT1 receptors in the central development of MSO-induced hypothermia in the restrained rat.
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PMID:Involvement of serotonin receptors in methionine sulfoximine-induced hypothermia in the rat. 135 3

The effects of submaximal and maximal thermogenic doses of isoproterenol (ISO) on operant thermoregulatory responses in a cold (-8 degrees C) environment were tested in lean (+/?) Zucker rats trained to barpress for radiant heat. Contrary to expectations, ISO rats pressed for twice as much exogenous heat as controls, but showed a smaller rise in colonic temperature. Conversely, a beta 3-selective adrenergic agonist (RO40-2148) decreased the requirement for exogenous heat and produced larger rises in colonic temperature. RO40-2148 and another beta 3-agonist (ICI D7114) produced similar responses in obese (fa/fa) Zucker rats, but tests with ISO were terminated because it caused profound, and lethal hypothermia. The hypothermic effects of ISO on colonic temperature were also observed in Sprague-Dawley rats at room temperature (22 degrees C), whereas RO40-2148 produced hyperthermia. These results provide behavioral evidence for the high thermogenic selectivity of these novel adrenergic agonists and support the existence of an atypical beta 3-adrenoceptor. The hypothermic effects of ISO are presumed to be due to actions on beta 1- and/or beta 2-adrenoceptors.
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PMID:Effect of conventional (mixed beta 1/beta 2) and novel (beta 3) adrenergic agonists on thermoregulatory behavior. 168 63

This study measured the velocity of the fast anterograde axonal transport of [3H]-proline-labelled proteins in sciatic motoneurones of rats with streptozotocin diabetes of 12 weeks duration and in age matched controls. Four groups of diabetic animals were studied. One of these groups remained untreated whilst 2 diabetic groups received a long-acting insulin twice weekly to limit body wasting, but to permit regular hyperglycaemia. One insulin-treated group and one other diabetic group received an aldose reductase inhibitor, "Statil" (ICI 128436) by dietary admixture. Neither diabetes alone nor any of the treatment regimes produced any significant alteration of axonal transport velocity. Sciatic nerve temperature was measured concomitantly. A slight nerve hypothermia was seen in the untreated diabetic rats, but not in either insulin-treated group. It is concluded that 2 aspects of diabetes mellitus, namely persistent hyperglycaemia and polyol pathway activity in nervous tissue are without effect on the velocity of fast orthograde axonal transport of proteins.
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PMID:Fast anterograde axonal transport in wasted and non-wasted diabetic rats; effects of aldose reductase inhibition. 243 44

The effects of single and chronic doses of rolipram on the sensitivity of alpha 2-adrenoceptors have been compared with the phosphodiesterase inhibitors, isobutylmethylxanthine (IBMX) and ICI 63,197, and the antidepressant, desipramine. While pretreatment with a single dose of rolipram, ICI 63,197 or IBMX administered either 1 or 24 h prior to clonidine (0.1 mg/kg) enhanced clonidine-induced hypothermia and hypoactivity, chronic dosing (twice daily for 14 days) with desipramine (10 mg/kg) or rolipram (5 mg/kg) antagonized these behavioural effects. In contrast, chronic dosing with IBMX or ICI 63,197 failed to antagonize clonidine-induced hypothermia and hypoactivity. In binding studies neither ICI 63,197, IBMX, rolipram nor desipramine induced changes in the binding of 3H-labelled clonidine to rat cerebral cortical membranes following chronic administration. The failure of ICI 63,107 and IBMX to antagonize clonidine-induced hypothermia and hypoactivity suggests that the antidepressant effect of rolipram is independent of its phosphodiesterase inhibitor property.
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PMID:Effect of long-term rolipram administration on the sensitivity of alpha 2-adrenoceptors in rat brain. 245 98

The effects of microinjections of thyrotropin-releasing hormone (TRH), neurotensin and ICI 174864 into the nucleus accumbens, nucleus caudatus, septum and mesencephalic periaqueductal grey were studied on ethanol-induced narcosis in the rat. Levels of narcosis were assessed by alterations in ethanol-induced hypothermia and sleep time. Ethanol produces a 2 degree C fall in body temperature over the first hour which then recovered over the next 2 h. Sedation was produced to the extent that the righting reflex was lost for between 80 and 90 min. In the nucleus caudatus all 3 peptides were ineffective at altering narcosis. In the periaqueductal grey, septum and accumbens, TRH (5 micrograms) and ICI 174864 (1 microgram) microinjections significantly reduced the sleep time by between 50 and 70%. ICI 174864 was approximately 10 times more potent that TRH at reducing the sleep time. In addition, both these peptides significantly accelerated the recovery from the ethanol-induced hypothermia in the periaqueductal grey, septum and accumbens. ICI 174864 prevented the ethanol-induced fall in body temperature. Neurotensin (5 micrograms) significantly increased the sleep time by up to 50% and potentiated the ethanol-induced hypothermia. These results suggest that the administration of TRH or the blockade of delta-opioid receptors, resulting in an inhibition of endogenous enkephalin transmission, may significantly inhibit ethanol narcosis in the rat. Opposing this, the application of neurotensin appears to potentiate ethanol narcosis. These results also indicate that endogenous enkephalin release plays an important role in ethanol narcosis.
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PMID:The effect of neurotensin, TRH and the delta-opioid receptor antagonist ICI 174864 on alcohol-induced narcosis in rats. 282 97

Antagonism of reserpine-induced hypothermia is an animal model used in the screening of antidepressants. The activity of imipramine on this test is partly impaired by propranolol. This effect of imipramine was analyzed using specific adrenoceptor and 5-HT receptor blocking drugs in order to determine the nature of this effect of propranolol. The non-selective beta 1-beta 2 adrenoceptor antagonist, propranolol as the specific beta 1 adrenoceptor antagonist betaxolol, but not the specific beta 2 blocking drug DL-erythro-3-isopropylamino-1-(7-methyl-4-indanyloxy)-2-butanol hydrochloride 313.9 (ICI 118,551), partly antagonized the effect of imipramine at 30 min. None of the serotonin (5-HT) receptor antagonists, methysergide, metergoline, ritanserin and buspirone, impaired the effect of imipramine. On the contrary, methysergide alone antagonized reserpine-induced hypothermia and methysergide or metergoline increased the action of imipramine. Propranolol impaired neither the hypothermia induced by an agonist at the 5-HT 1A receptors: 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) nor the increase in spontaneous motor activity induced by an agonist at the 5-HT 1B receptors: 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (Ru 24,969). It is concluded that the effect of propranolol is not the result of a blockade of 5-HT 1A, 5-HT 1B or 5-HT 2, but is in part due to blockade of beta 1 adrenoceptors.
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PMID:Analysis of the nature of antagonism of the reserpine-induced hypothermia by imipramine. 289 Oct 45

The antidepressant potential of rolipram and inhibitors of phosphodiesterase (PDE) which are selective for cyclic AMP has previously been ascribed to enhancement of central noradrenergic transmission by the combination of two mechanisms of action: increase of synthesis of noradrenaline and release (presynaptic component) and concomitant potentiation of noradrenaline signals due to inhibition of phosphodiesterase (postsynaptic component). To examine the contribution of the latter component to the antidepressant action, rolipram, ICI 63 197 or Ro 20-1724 were given to mice which were depleted of monoamines in the brain by combined pretreatment with reserpine, alpha-methyl-p-tyrosine and p-chlorophenylalanine. Rolipram, ICI 63 197 and Ro 20-1724 dose-dependently reversed the hypothermia and hypokinesia induced by this pretreatment. Imipramine and pargyline were inactive in this respect, indicating that their antidepressant effect depends on the availability of endogenous monoamines. The antihypothermic and antihypokinetic action of rolipram was not prevented by blockade of central beta-adrenergic or dopaminergic receptors. It is concluded that an action of rolipram, beyond postsynaptic receptors, essentially contributes to its antidepressant effect. The postsynaptic adenylate cyclase/cyclic AMP phosphodiesterase system is thought to be the most likely target. The unique properties of rolipram to stimulate both presynaptic and postsynaptic components of central neurotransmission should enable more efficient transduction of postsynaptic signals by circumventing presynaptic inhibitory feedback mechanisms, responsible for the delay in the therapeutic action of conventional antidepressant drugs.
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PMID:Rolipram, a novel antidepressant drug, reverses the hypothermia and hypokinesia of monoamine-depleted mice by an action beyond postsynaptic monoamine receptors. 294 76

We studied the in vivo pharmacology of a selective agonist (DPDPE) and a selective antagonist (ICI 174864) at delta opioid receptors. ICI 174864 (10 micrograms icv) caused postural abnormalities, barrel rotation and hypothermia in rats. DPDPE induced behavioural arousal (at 75 micrograms icv) and barrel rotation (at 125 micrograms) in rats. ICI 174864 (10 micrograms icv) attenuated acetic acid induced writhing in mice. This action was antagonized by naloxone (10 but not 2 mg/kg s.c.). A lower, non-agonist dose of ICI 174864 (5 micrograms) antagonized DPDPE (3 micrograms icv) in this test without affecting DAGO (0.0006 micrograms icv), a selective agonist at mu receptors. In the mouse tail flick test, ICI 174864 (10-50 micrograms icv) did not significantly antagonize the agonist actions of DPDPE (40 micrograms icv) or DAGO (0.3 micrograms icv). At 10-50 micrograms icv, ICI 174864 had no marked effect on gastrointestinal transit in mice. ICI 174864 (25 micrograms icv or 20 mg/kg s.c.) did not interact with mu opioid receptors in mice rendered physically dependent on morphine.
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PMID:Studies in vivo with ICI 174864 and [D-Pen2, D-Pen5]enkephalin. 298 31

In mice, reserpine-induced hypothermia is partly antagonized by clenbuterol, a beta-adrenergic agonist specific for beta 2 receptors, and completely antagonized by dobutamine, a beta-adrenergic agonist specific for beta 1 receptors. In addition, the effects of dobutamine and of clenbuterol are impaired by betaxolol (1 and 4 mg/kg) and unchanged by ICI 118,551 (1 and 4 mg/kg) beta-blocking drugs respectively selective for beta 1 and beta 2 receptors. These results indicate that reserpine-induced hypothermia depends on the beta 1 receptors and lend support to an indirect effect of clenbuterol. After a chronic treatment, clenbuterol-induced antagonism of reserpine hypothermia is facilitated. This facilitation is impaired by ICI 118,551 and by betaxolol but, in this last case, with high doses only. So the facilitation involves beta 2 adrenergic receptors and implies an increase in the sensitivity of beta 1 receptors.
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PMID:Reserpine-induced hypothermia: participation of beta 1 and beta 2 adrenergic receptors. 303 39

The significance of a characteristic symptomatology (hypothermia, hypoactivity, forepaw shaking, grooming, head twitches) as a potential in vivo correlate of enhanced availability of brain adenosine cyclic 3',5'-monophosphate (cAMP) was examined in rats following systemic administration of various doses of dibutyryladenosine cAMP (dBcAMP) or of the phosphodiesterase (PDE) inhibitors rolipram, Ro 20-1724, ICI 63-197, isobutylmethylxanthine (IBMX) theophylline, cartazolate, and papaverine. The various PDE inhibitors could be assigned to three groups according to the pattern of behavioral alterations they induced. Rolipram, Ro 20-1724, and ICI 63-197 (group 1) caused hypothermia, hypoactivity, forepaw shaking, grooming, and head twitches. All behavioral effects were mimicked by dBcAMP but not dBcGMP. The order of potency and effective dosage range to induce the behavioral alterations were, in descending order, rolipram (0.09-1453 mumol/kg IP), ICI 63-197 (0.48-119 mumol/kg IP), Ro 20-1724 (5.6-1438 mumol/kg IP), corresponding with the recently reported efficacy of the drugs to elevate rat brain cAMP in vivo. Comparatively high doses of the alkylxanthine PDE inhibitors IBMX and theophylline (group 2) caused hypothermia, forepaw shaking, grooming, and head twitches concomitantly with a decline of the motor stimulatory effect, suggesting enhanced availability of brain cAMP. The order of potency and the effective dosage range to induce the behavioral alterations were, in descending order, IBMX (28.1-113 mumol/kg IP) and theophylline (139-555 mumol/kg IP). The third group, papaverine (295-1179 mumol/kg IP) and cartazolate (21.5-345 mumol/kg IP), caused only hypothermia and hypoactivity. The differences in the behavioral pattern of the two latter groups of compounds in comparison with dBcAMP and the selective cAMP PDE inhibitors are discussed with regard to their additional interference with adenosine actions besides their nonselective PDE inhibitory action.
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PMID:Characteristic behavioural alterations in rats induced by rolipram and other selective adenosine cyclic 3', 5'-monophosphate phosphodiesterase inhibitors. 618 75


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