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)

gamma-Aminobutyric acid (GABA) intraperitoneally injected (i.p.) produced a dose-dependent hypothermia in restrained rats. GABA-induced hypothermia (1000 mg kg-1) was antagonized by pretreatment with atropine (2.5 and 10 mg kg-1 i.p.), hyoscine butylbromide (2.5 mg kg-1 i.p.), hexamethonium (0.75 mg kg-1 i.p.) or physostigmine (0.2 mg kg-1 s.c.). Hexamethonium (7.5 mg kg-1 i.p.) did not influence the hypothermia induced by GABA. The antagonism by physostigmine of GABA-induced hypothermia was attenuated by pretreatment of the rats with either alpha-methyl-p-tyrosine (200 mg kg-1 i.p.) or hexamethonium (7.5 mg kg-1 i.p.), but it was potentiated by either atropine (5 mg kg-1 i.p.) or hexamethonium (0.75 mg kg-1 i.p.). The data indicate that GABA-induced hypothermia may be partly mediated by acetylcholine release. Muscarinic receptors may play an important role in the effect of GABA. The results support the hypothesis of nicotinic presynaptic receptors modulating noradrenergic nerve endings that play a part in the hypothermic response of GABA.
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PMID:Hypothermic effect of GABA in conscious stressed rats: its modification by cholinergic agonists and antagonists. 289 Jul 37

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 ability of the selective cyclic mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), to inhibit the acute and chronic effects of morphine in vivo was studied in mice. Intracerebroventricular (i.c.v.) administration of CTOP antagonized the analgesic effect of morphine in a dose-dependent manner, as measured by the heat-irradiant (tail-flick) method. CTOP was more effective than naloxone in inhibiting analgesia on a molar basis. CTOP also antagonized the acute morphine-induced hypermotility. CTOP caused withdrawal hypothermia and a loss of body weight in morphine-dependent animals. After the development of morphine-induced chronic dependence, CTOP administered i.c.v. caused a dose-dependent loss of body weight and hypothermia, and was about 10-400 times more potent than naloxone. CTOP administered alone to drugnaive mice did not cause antinociception, changes in body weight or body temperature.
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PMID:Central effects of the potent and highly selective mu opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) in mice. 290 58

The effects of the novel veterinary sedative, medetomidine, were studied in rats. In addition to a dose-dependent sedation, which at high doses (greater than 100 micrograms/kg) included loss of the righting reflex and hypothermia, there was a concurrent decrease in the turnover rate of biogenic amines in the brain. Noradrenaline turnover was dose dependently decreased as judged by (i) the decrease in the brain concentration of its metabolite, MHPG-SO4, (ii) a decrease in the ability of alpha-methyl-p-tyrosine methyl ester to deplete brain noradrenaline stores and (iii) a dose-dependent decrease in the level of unconjugated MHPG in the CSF of freely moving rats. Brain dopamine turnover was also inhibited at higher doses as judged by the alpha-methyl-p-tyrosine method and by a decrease in the concentration of HVA in the rat brain 4 h after medetomidine. Serotonin turnover as estimated by the ratio of biogenic amine to its metabolite was also significantly depressed. These changes in brain biogenic amine turnover were inhibited by prior or simultaneous administration of alpha 2-adrenoceptor antagonists, either yohimbine or the more specific, novel alpha 2-antagonist, atipamezole.
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PMID:Behavioural and neurochemical effects of medetomidine, a novel veterinary sedative. 290 7

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

Forskolin, a direct activator of the catalytic subunit of adenylate cyclase (AC), and the cyclic nucleotide analogs dibutyryl cAMP (dBcAMP), 8-bromo cAMP (8-BrcAMP) and dibutyryl cGMP (dBcGMP) were tested for their ability to reverse the hypothermia or hypokinesia of mice depleted of presynaptic endogenous monoamines by pretreatment with reserpine, alpha-methyl-p-tyrosine and p-chlorophenylalanine. Forskolin and the cAMP analogs decreased the rectal temperature and inhibited locomotor activity in normal mice. In mice depleted of brain monoamines forskolin reversed the hypothermia and hypokinesia; dBcAMP and 8-BrcAMP antagonized the hypothermia but were only marginally effective in reversing the hypokinesia. DBcGMP was inactive. The antihypothermic action of forskolin or salbutamol was enhanced by the novel antidepressant and cAMP selective phosphodiesterase inhibitor rolipram (4RS-[3-cyclopentyloxy-4-methoxy-phenyl]-2-pyrrolidone). As an indirect effect via release of endogenous monoamines stimulating postsynaptic receptors was precluded by the monoamine-depleting pretreatment, forskolin and the cAMP analogs are thought to exert their antidepressant action by directly increasing brain cAMP availability. This is achieved by forskolin via activation of the catalytic subunit of AC and by the cAMP analogs via substitution for cAMP. These findings suggest that antidepressant activity is crucially linked to enhanced cAMP availability within brain effector cells. The successful treatment of endogenously depressed patients with rolipram supports this assumption.
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PMID:Effects of forskolin and cyclic nucleotides in animal models predictive of antidepressant activity: interactions with rolipram. 302 33

Gamma-aminobutyric acid (GABA) was injected intraperitoneally (i.p.) in conscious restrained rats and the effects on core temperature were observed. GABA (250-1000 mg/kg) produced a dose-dependent decrease in core temperature at an ambient temperature of 22 +/- 1 degree C. GABA-induced hypothermia (1000 mg/kg) was attenuated by pretreatment with reserpine (2 mg/kg, i.p.), p-chloro-phenyl-alanine (300 mg/kg, i.p.), yohimbine (0.25 mg/kg, i.p.) or methysergide (2.5 mg/kg, i.p.). Neither alpha-methyl-p-tyrosine (200 mg/kg, i.p.), nor phenoxybenzamine (5 mg/kg, i.p.), nor pimozide (0.5 mg/kg i.p.) antagonized GABA-induced hypothermia. Pretreatment with either propranolol (10 mg/kg, i.p.) or bicuculline (3 mg/kg, i.p.) potentiated hypothermia induced by GABA. It is concluded that hypothermia produced by i.p. injection of GABA could be due to release of serotonin by activation of bicuculline-insensitive GABA receptors located on central serotonergic neurons.
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PMID:Hypothermic effect of GABA in conscious restrained rats and its modification by monoaminergic blocking drugs. 360 97

Short-lasting decrease in rectal temperature in mice after intraperitoneal administration of an enkephalin dimer, the so called double-enkephalin--(Tyr-D-Ala-Gly-Phe-NH)2 (D-ENK-O)--at dose 0.1, 0.5, 1, 2.5, 5, 10 and 20 mg/kg of body weight was observed. Another double-enkephalin--Tyr-D-Ala-Gly-Phe-NH-(CH2)3-HN-Phe-Gly-D-Ala-Tyr-- fai led to produce this effect. The hypothermic effect of D-ENK-O was almost completely reduced by naloxone which suggests an involvement of opiate receptors in the D-ENK-O produced hypothermia in mice.
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PMID:The effect of enkephalin dimers on body temperature in mice. 365 11

Dependent upon the route and/or site of administration, arginine vasopressin (AVP) evoked a number of thermoregulatory actions in the conscious rat. Infused into a lateral cerebral ventricle, arginine vasopressin produced short-lasting hypothermia of rapid onset. Injected into the preoptic area, arginine vasopressin caused long-lasting hyperthermia of rapid onset that was antagonized by the prior administration of a V1 receptor antagonist, [d(CH2)5 Tyr(Me)AVP]. Injections of arginine vasopressin into the nucleus accumbens, ventral septal area, substantia innominata and the dorsomedial hypothalamus were without effect on body temperature. Although the antipyretic action of arginine vasopressin within the ventral septal area has been well documented, these findings provide further evidence that this peptide exerts additional thermoregulatory actions that are both neuroanatomically and functionally specific.
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PMID:Thermoregulatory actions of centrally-administered vasopressin in the rat. 374 27

Further information about the nicotine-induced changes in striatal dopamine metabolism in hypothermic mice was searched by measuring the contents of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; 3-methoxytyramine, 3-MT; and homovanillic acid, HVA) after blocking the synthesis of dopamine by alpha-methyl-p-tyrosine (alpha-MT). This method gave a possibility to study the effect of nicotine on the metabolism of dopamine in two pools (the cytoplasmic "newly-synthesized" dopamine and the granular dopamine). 3 mg/kg of (-)nicotine was given s.c. four times, at 110, 80, 50 and 20 min, and alpha-MT (250 mg/kg i.p.) at 60 min before sacrifice. To prevent the peripheral effects of nicotine all mice were given hexamethonium (10 mg/kg i.p.) at 140 min before sacrifice. Hexamethonium did not alter striatal dopamine metabolism. Experiments were performed at 20-22 degrees C at which temperature nicotine induced hypothermia or at 32-34 degrees C. The alpha-MT-induced proportional decrease of 3-MT content was clearly less than that of dopamine content. On the contrary the alpha-MT treatment decreased the DOPAC content proportionally more than the dopamine content. Thus DOPAC could not be solely formed from the same dopamine pool as 3-MT. These results indicate that 3-MT reflects best the metabolism of the granular dopamine and DOPAC that of the "newly-synthesized" dopamine. In hypothermic mice nicotine administration reduced the alpha-MT-induced depletion of the dopamine content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different changes in striatal dopamine metabolism induced by nicotine in mice kept at different ambient temperatures. Evidence for partly separate metabolic routes of dopamine derived from separate compartmentations. 382 29


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