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

The results of our recent investigations have suggested that tolerance and cross-tolerance development to motor-impairing and hypothermic effects of ethanol was slowed when brain serotonin (5-HT) was extensively depleted by treatment with p-chlorophenylalanine (p-CPA). These findings have been extended by the observation that p-PCA also slowed the development of tolerance to motor-impairing effects of barbital whether tolerance was tested repeatedly in the same animal or in separate subgroups being tested only once. Additional support was provided by the demonstration that intracerebral injection of 5,7-dihydroxytryptamine (-DHT), which is known to deplete 5-HT markedly, also slowed the development of tolerance to motor-impairing and hypothermic effects of ethanol. In addition, when brain 5-HT level was elevated by administration of L-tryptophan, the rate of tolerance development to ethanol, as measured by motor impairment and hypothermia, was accelerated. In contrast to 5,7-DHT, intracerebral injection of 5,6-DHT was surprisingly found to accelerate the development of tolerance to ethanol. Upon further investigation, however, it was determined that the 5,6-DHT treatment depleted brain 5-HT levels by only 20% and, in addition, resulted in the development of supersensitivity. These results further confirm and extend the generality of our observations that 5-HT may be involved in the development of tolerance and cross-tolerance to sedatives. The possibility of a non-specific vs. specific effect of the serotoninergic system (as well as other aminergic systems) in tolerance and neuroplasticity deserves further investigation. The possible significance of these findings and the role of 5-HT (and noradrenaline) in the mechanism of tolerance are discussed in terms of analogy to enzyme or receptor mechanism.
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PMID:Role of serotonin in tolerance to ethanol and barbiturates: evidence for a specific vs. non-specific concept of tolerance. 16 Aug 66

Elevating serotonin (5-HT) contents in brain with 5-hydroxytryptophan (5-HTP) reduced rectal temperature (Tre) in rabbits after peripheral decarboxylase inhibition with the aromatic-L-amino-acid decarboxylase inhibitor R04-4602 at two ambient temperatures (Ta), 2 and 22 degrees C. The hypothermia was brought about by both an increase in respiratory evaporative heat loss (Eres) and a decrease in metabolic rate (MR) in the cold. At a Ta of 22 degrees C, the hypothermia was achieved solely due to an increase in heat loss. Depleting brain contents of 5-HT with intraventricular, 5,7-dihydroxytryptamine (5,7-DHT) produced an increased Eres and ear blood flow even at Ta of 2 degrees C. Also, MR increased at all but the Ta of 32 degrees C. However, depleting the central and peripheral contents of 5-HT with p-chlorophenylalanine (pCPA) produced lower MR accompanied by lower Eres in the cold compared to the untreated control. Both groups of pCPA-treated and 5,7-DHT-treated animals maintained their Tre within normal limits. The data suggest that changes in 5-HT content in brain affects the MR of rabbits in the cold. Elevating brain content of 5-HT tends to depress the MR response to cold, while depleting brain content of 5-HT tends to enhance the MR response to cold.
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PMID:Changes in serotonin contents in brain affect metabolic heat production of rabbits in cold. 30 17

Role of brain monoamines in the hyprothermic activity of cannabis resin (CI) in albino rats was studied using agents which influence monoamine synthesis, storage, release, reuptake, metabolism and receptor activity and monoaminergic neuronal activity. Delta-9-tetrahydrocannabinol content of resin was estimated to be 17%. Reserpine was used for comparison. CI was given orally in the dose of 50 mg/kg. Nialamide (NM) and alpha-methyl-metatyrosine (MMT) caused slight hyperthermia. p-Chlorophenylalanine (PCPA), alpha-methol-p-tyrosine (MPT), 5,6-dihydroxytryptamine (DHT, icv) and 6-hydroxydopamine (6-HD, icv) had no effect on body temperature. alpha-Methyl-dopa (m-Dopa), diethyldithiocarbamate (DDC), DDC with l-Dopa, gammabutyrolactone (GBL), phentolamine (PHENT), phenoxybenzamine (PBZ), propranolol (PROP) and imipramine (IMP) produced hypothermia. Hyprothermic activity of CI was potentiated by NM and PCPA, unaffected by DHT and m-Dopa, blocked by MMT, MPT, 6-HD, GBL, PHENT, PROP and chlorpromazine (CPZ), inhibited by DDC, DDC and l-Dopa and PBZ. CI induced hyperthermia in tolerant rats could be reversed to hypothermia by IMP. Reserpine hypothermia was blocked by NM, MPT, 6-HD and CPZ. There was a partial cross tolerance between cannabis and reserpine. Studies indicate that the hypothermic activity of CI similar to that of reserpine is mediated through central catecholamines and not 5-HT, and that noradrenaline is involved and not dopamine. However, the mechanism of action of cannabis and reserpine on noradrenergic neurone seems to be different.
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PMID:Role of catecholamines in the hypothermic activity of cannabis in albino rats. 82 62

1. Parallel series of experiments were carried out in the rat and mouse in order to investigate the mechanism(s) underlying the hypothermia induced in rodents by the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 2. In the mouse, lesioning of central 5-hydroxytryptaminergic neurones (by use of the neurotoxin, 5,7-dihydroxytryptamine; 5,7-DHT) abolished the hypothermic response to 8-OH-DPAT, and depletion of brain 5-hydroxytryptamine (5-HT) levels (with the 5-HT synthesis inhibitor, p-chlorophenylalanine) markedly attenuated the response in this species. These pretreatments did not significantly attenuate 8-OH-DPAT-induced hypothermia in the rat, except for a significant attenuation of the response in 5,7-DHT-lesioned rats at the top dose of 8-OH-DPAT (1.0 mg kg-1, s.c.). 3. Pharmacological pretreatments which facilitate 5-HT release (selective 5-HT uptake inhibitors, precursor (5-hydroxytryptophan) loading, or fenfluramine), markedly attenuated or abolished 8-OH-DPAT-induced hypothermia in the mouse. These pretreatments generally had no significant effect on 8-OH-DPAT-induced hypothermia in the rat. 4. The selective noradrenaline uptake inhibitor, desipramine, had no effect on the hypothermic response to 8-OH-DPAT in either species. The selective dopamine uptake inhibitor, nomifensin, significantly increased the hypothermic response to 8-OH-DPAT in the mouse, but did not affect the response in the rat except at high, motor stimulant doses, when the response was attenuated. 5. These data are consistent with the hypothesis that 8-OH-DPAT-induced hypothermia is mediated by presynaptic autoreceptors in the mouse and by postsynaptic 5-HT1A receptors in the rat. Preliminary data also indicate an involvement of dopamine release in the mouse but not in the rat.
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PMID:Direct evidence for an important species difference in the mechanism of 8-OH-DPAT-induced hypothermia. 183 17

There have been few studies investigating the effect of treatments that alter serotonergic neurotransmission on the density of serotonin1A (5-hydroxytryptamine1A [5-HT1A]) receptors, even though lesioning serotonergic neurons has been reported to enhance certain responses thought to be due to activation of 5-HT1A receptors and repeated treatment of rats with different types of antidepressants can diminish 5-HT1A-mediated responses. Consequently, the binding of 3H-8-hydroxy-2-(di-n-propylamino)-tetralin (DPAT) to 5-HT1A receptors in serotonergic cell body and terminal field areas of rat brain was measured by quantitative autoradiography following either the lesioning of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT), or after chronic administration of monoamine oxidase inhibitors (MAOIs) (clorgyline, phenelzine, or tranylcypromine) or inhibitors of 5-HT uptake (citalopram or sertraline). Treatment of rats with 5,7-DHT did not cause any significant increase in binding of 3H-DPAT to 5-HT1A receptors in any area of the brain examined. There was no significant reduction in the binding of 3H-DPAT in terminal field areas of serotonergic innervation in rats treated with 5,7-DHT except in the CA2/CA3 region of the hippocampus (33% to 35% reduction). In the dorsal and median raphe nuclei, the specific binding of 3H-DPAT was reduced by treatment of rats with 5,7-DHT. In lesioned rats, the binding of 3H-cyanoimipramine (3H-CN-IMI) to uptake sites for serotonin was essentially eliminated in all terminal field areas examined, as well as in the dorsal and median raphe nuclei. Repeated administration of clorgyline, phenelzine, tranylcypromine, citalopram, or sertraline produced an attenuation of the hypothermic response of rats to acute subcutaneous injection of the 5-HT1A-receptor-agonist DPAT. In spite of this change in 5-HT1A responsivity, these treatments caused in the same animals no consistent change in the binding of 3H-DPAT in either serotonergic cell body or terminal field areas. Of the five drugs studied that diminished DPAT-induced hypothermia, only phenelzine and clorgyline significantly reduced the binding of 3H-DPAT, and even then in only a few of the 12 areas of brain measured. As a result of treatment of rats with tranylcypromine there was a significant increase in the binding of 3H-DPAT in the CA2/CA3 region of the hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A quantitative autoradiographic study of serotonin1A receptor regulation. Effect of 5,7-dihydroxytryptamine and antidepressant treatments. 202 79

Acute clenbuterol, a beta-adrenergic stimulant, decreases motility and antagonizes reserpine-induced hypothermia in mice. After repeated treatment with clenbuterol, the hypomotility disappears (tolerance) but the antagonism of reserpine-induced hypothermia increases (facilitation). To investigate the function of serotonin in tolerance and facilitation, lesions of the serotonergic system were performed by intracerebroventricular administration of the neurotoxin 5,7 dihydroxytryptamine (5,7-DHT). After lesions of the serotonergic system, the tolerance to clenbuterol-induced hypomotility persists, but the facilitation of the antagonism by clenbuterol of reserpine-induced hypothermia disappears. Thus, the serotonergic nerve terminals must be intact for the latter but not the former response to occur. Since the reversal of reserpine-induced hypothermia in animals is predictive of antidepressant effects in man, it is suggested that the therapeutic action of clenbuterol in depressed patients may be mediated through the serotonergic system.
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PMID:Lesions of the serotonergic system impair the facilitation of but not the tolerance to the effects of chronic clenbuterol administration. 243 13

Are ascending noradrenergic and serotonergic pathways necessary for effects of electroconvulsive treatment? Clonidine hypothermia and forced swim study. W. DANYSZ , W. KOSTOWSKI, M. HAUPTMANN, A. BIDZINSKI. Pol. J. Pharmacol. Pharm., 1989, 41, 15-22. Influence of chemical lesions to the noradrenergic locus coeruleus (intracerebral 6-OHDA injection, systemic administration of DSP-4) and serotonergic raphe system (intracerebral 5,7-DHT) on some effects produced by electroconvulsive shock (ECS) was studied. Administration of ECS slightly but significantly attenuated clonidine (CLO)-induced hypothermia and reduced rats immobility in forced swim test. DSP-4 reduced ECS action on CLO hypothermia remaining without effect upon ECS action in the second test. Other lesions were ineffective in both tests. This finding is in contrast to results obtained previously in animals receiving desipramine. The possible difference between ECS and antidepressant drugs action is discussed.
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PMID:Are ascending noradrenergic and serotonergic pathways necessary for effects of electroconvulsive treatment? Clonidine hypothermia and forced swim study. 251 61

In the mouse, injection (subcutaneously) of the putative 5-HT1 agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), produced a dose-related hypothermia (ED50:0.36 mg/kg). A maximum response was elicited by intracerebroventricular (i.c.v.) injection of 8-OH-DPAT (3 micrograms) and almost abolished by lesion of 5-HT-containing terminals in the brain with 5,7-dihydroxytryptamine (5,7-DHT; i.c.v.) or long-term treatment with p-chlorophenylalanine. The response was unaltered by a range of neurotransmitter antagonists: prazosin (alpha1-adrenoceptor), idazoxan (alpha2-adrenoceptor), metoprolol (beta1-adrenoceptor), erythro-DL-1-(7-methylindan-4-yloxy)-3-isopropylamino-but an-2-ol (beta2-adrenoceptor), (-)propranolol or (+/-)pindolol (beta-adrenoceptor), flupenthixol (dopamine) or Ro 15-1788 (benzodiazepine binding site). Classical 5-HT antagonists (methysergide, metergoline, cinanserin and methiothepin) were either without effect or facilitated the response and the 5-HT2 antagonist, ritanserin was also without effect. In contrast, quipazine and haloperidol produced a dose-related antagonism of the response. Since the response was almost abolished by a lesion induced by 5,7-DHT and was antagonised by quipazine, which is known to antagonise presynaptic 5-HT function in vitro, it is suggested that the hypothermic response is due to 8-OH-DPAT acting as an agonist at a presynaptic 5-HT receptor, which also appears to be sensitive to butyrophenones (the antagonism elicited by haloperidol but not by flupenthixol). The hypothermic response of mice to 8-OH-DPAT, therefore, may provide a simple and convenient in vivo model in which to measure the function of the presynaptic 5-HT receptor.
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PMID:The pharmacology of the hypothermic response in mice to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). A model of presynaptic 5-HT1 function. 286 35

The hypothermic and motor behavioural responses to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been investigated in the rat. The dose-effect relationship showed that hypothermia appeared at a lower dose than a definite motor syndrome. The hypothermic response to 8-OH-DPAT was attenuated following depletion of 5-hydroxytryptamine (5-HT) by repeated intraperitoneal (IP) administration of parachlorophenylalanine (200 mg/kg) or by injection of 5,7-dihydroxytryptamine (5,7-DHT, 100 micrograms) into the region of the third ventricle; the motor behavioural response produced simultaneously was not. Indeed, after 5,7-DHT, it was increased. Quipazine (1 mg/kg, IP) antagonised the hypothermic response and facilitated the motor behaviour. Clenbuterol (2.5 mg/kg, IP) increased both hypothermic and motor responses. (+/-)-propranolol was without effect on the simple hypermotility produced by 8-OH-DPAT, although it is known to antagonise the hypothermic and stereotyped motor responses. It is concluded that 8-OH-DPAT probably produces its hypothermic effects by actions at 5-HT receptors located presynaptically on 5-HT neurones, while the stereotyped components of the serotonin syndrome appear to be mediated by post-synaptic receptors.
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PMID:The pharmacology of the behavioural and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 295 79

The putative 5-HT1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY165163, PAPP) (1, 2, 4, 10 mg/kg s.c.) caused a significant and dose-dependent hypothermia in rats, 30 and 60 min after injection. The decreases of temperature were less marked than that caused by 8-OH-DPAT 1 mg/kg s.c.). Depletion of brain serotonin (5-HT) by 91% following pretreatment with p-chlorophenylalanine (pCPA) (150 mg/kg i.p. on three successive days) significantly enhanced the hypothermic effects of both 8-OH-DPAT (0.25 mg/kg s.c.) and LY165163 (4 mg/kg s.c.). LY165163-induced hypothermia was also somewhat enhanced following depletion of hypothalamic 5-HT by 76% after infusion of 5,7-dihydroxytryptamine (5,7-DHT) (150 micrograms) into the third ventricle. Results indicate that the hypothermia induced by the putative 5-HT1A agonists LY165163 and 8-OH-DPAT in the rat is not dependent on presynaptic 5-HT stores and is therefore probably mediated by postsynaptic 5-HT receptors.
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PMID:Hypothermia induced by the putative 5-HT1A agonists LY165163 and 8-OH-DPAT is not prevented by 5-HT depletion. 296 83


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