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)

Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor with therapeutic benefit in patients with obsessive-compulsive disorder (OCD). To evaluate the effect of chronic FLX treatment on 5-HT1A receptor responsivity, hypothermic, neuroendocrine, and behavioral responses to the selective 5-HT1A receptor ligand ipsapirone (IPS) were examined in patients with primary OCD. A single dose of 0.3 mg/kg of IPS or placebo were given under double-blind, random-assignment conditions to ten patients before and during FLX treatment. The ability of IPS to induce hypothermia and ACTH/cortisol release was significantly attenuated during chronic FLX as compared to the pretreatment IPS challenge. The behavioral effects of IPS, though minimal, were less pronounced during FLX treatment. While FLX was effective in reducing the severity of OC symptoms, no significant correlation between attenuation of 5-HT1A receptor-mediated functional measures and FLX-induced improvement in OC symptoms was detected. These findings are consistent with the development of adaptive hyporesponsivity of the 5-HT1A receptor-effector system complex possibly involving subsensitivity of the 5-HT1A receptor itself and/or decreased functional activity of the postreceptor signal transduction. Modulation of 5-HT1A receptor-effector system function may be critical to the antidepressant/anti-OC efficacy of 5-HT reuptake inhibitors.
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PMID:Long-term fluoxetine treatment decreases 5-HT1A receptor responsivity in obsessive-compulsive disorder. 168 17

1. Amphetamine-induced hypothermia in mice is facilitated by dopaminergic stimulation and 5-hydroxytryptaminergic inhibition. The present study was designed to investigate: (a) the involvement of other neuronal systems, such as the gamma-aminobutyric acid (GABA), the opioid and the cholecystokinin (CCK-8) systems; (b) the possible contribution of hydroxylated metabolites of amphetamine to the hypothermia; (c) the capacity of dopamine itself to induce hypothermia and its mechanisms, in order to clarify the resistance of amphetamine-induced hypothermia to certain neuroleptics. 2. Pretreatment with the GABA antagonists, bicuculline and picrotoxin, did not inhibit amphetamine-induced hypothermia. The GABAB agonist, baclofen (2.5 mg kg-1, i.p.) potentiated this hypothermia, whereas the GABAA agonist, muscimol, did not. gamma-Butyrolactone (GBL) (40 mg kg-1, i.p.) and the neuropeptide CCK-8 (0.04 mg kg-1, i.p.) also induced potentiation. The opioid antagonist, naloxone, was without effect. 3. Dopamine itself (3, 9, 16 and 27 micrograms, i.c.v.) induced less hypothermia than the same doses of amphetamine. Sulpiride did not block dopamine-induced hypothermia, but pimozide (4 mg kg-1, i.p.), cis(z)flupentixol (0.25 mg kg-1, i.p.) and haloperidol (5 micrograms, i.c.v.) did. The direct dopamine receptor agonist, apomorphine, did not alter the hypothermia. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the inhibitor of 5-HT synthesis, p-chlorophenylalanine (PCPA), modified dopamine-induced hypothermia. Fluoxetine, an inhibitor of 5-HT reuptake, had no effect, whereas quipazine (6 mg kg-1, i.p.), a 5-HT agonist, totally prevented the hypothermia. Hypothermia was unaffected by pretreatment with CCK-8. 4. These data indicate that the hypothermia induced by amphetamine involves not only dopaminergic and 5-hydroxytryptaminergic systems which are functionally antagonistic, but is also facilitated by direct or indirect GABA and CCK-8 receptor stimulation. This facilitation could result, in part, from modulation of dopaminergic neurotransmission. This may explain the apparent resistance of amphetamineinduced hypothermia to some neuroleptics, while dopamine-induced hypothermia is not resistant. The possible action of hydroxylated metabolites of amphetamine may also help to explain these differences.
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PMID:Facilitation of amphetamine-induced hypothermia in mice by GABA agonists and CCK-8. 185 28

To clarify the impact of hypothermia on the hormonal control of glucose metabolism, rats were rendered hypothermic (25 C) after catheterization of the portal vein. Glucose, insulin, glucagon, and catecholamine concentrations were serially monitored, and the regional blood flows were measured, allowing the estimation of hormone outputs. Hypothermia reduced the portal blood flow by 50% without changing arterial blood pressure, blood gases, or pH. Portal plasma insulin secretion dropped (0.05 +/- 0.01 vs. 0.23 +/- 0.04 mU/min), and glucagon secretion increased (0.81 +/- 0.18 vs. 0.38 +/- 0.10 ng/min). The B cell responses to glucose, arginine, and glucagon were abolished, while the A cell response to arginine was not significantly affected. Glucose intolerance was apparent after iv glucose or arginine loads. Haloperidol and to a lesser extent phentolamine suppressed the cold-induced glucagon rise. Phentolamine and to a lesser extent haloperidol alleviated the cold-induced suppression of insulin release. Propranolol, naloxone, and atropine were relatively inactive. The cold-induced glucose intolerance was not corrected by phentolamine treatment. A marked resistance to iv insulin was apparent in these rats, which is in contrast to a normal sensitivity to iv glucagon.
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PMID:Glucagon and insulin secretion and their biological activities in hypothermic rats. 643 6

One week after a single administration of 3,4-methylenedioxymethamphetamine (MDMA HCI, 30 mg/kg i.p.), 5-HT1A receptor density was significantly increased by approximately 25-30% in the frontal cortex and hypothalamus of rats. The increased density correlated with the potentiation of the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.) or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the depletion of 5-hydroxytryptamine (5-HT) induced by MDMA and also blocked the effects of this neurotoxin on 5-HT1A receptor density and on 8-OH-DPAT-induced hypothermia. The protection afforded by drugs against 5-HT loss did not correlate, however, with the antagonism of the acute hyperthermic effect of MDMA. The present results indicate that drugs able to prevent or to attenuate MDMA-induced 5-HT loss also prevent the changes in 5-HT1A receptor density as well as the enhanced hypothermic response to the 5-HT1A receptor agonist 8-OH-DPAT in MDMA-treated rats.
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PMID:MDMA ('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion. 965 58

1. It has been suggested that the dose of delta9-tetrahydrocannabinol (delta9-THC) that induces hypothermia in the rat increases the release of brain 5-hydroxytryptamine (5-HT). In light of this, we investigated the hypothermia produced by delta4-THC, and the effect the selective serotonin reuptake inhibitor fluoxetine has on this response. 2. A significant dose-dependent decrease in body temperature occurred after i.v. administration of 0.5 to 5 mg kg(-1) delta9-THC; maximum decreases being 0.8+/-0.2 degrees C to 2.9+/-0.3 degrees C. This hypothermic response was attenuated by the cannabinoid CB1 receptor antagonist SR 141716. 3. Fluoxetine (10 mg kg(-1) i.p.) alone caused a decrease in body temperature of 0.6+/-0.1 degrees C (n=32, P < 0.05) after 40 min. However, pretreatment with fluoxetine (10 mg kg(-1) i.p.) 40 min before delta9-THC significantly reduced the delta9-THC-induced hypothermia (n=7-8, P < 0.05). Contrary to this antagonist-like effect, fluoxetine administered 40 min after delta9-THC significantly potentiated the delta9-THC-induced hypothermia, producing a maximum decrease of 3.2+/-0.3 degrees C. 4. It is suggested that the effect of fluoxetine on the delta9-THC-induced hypothermic response is dependent on the time of its administration relative to that of delta9-THC. Pretreatment with fluoxetine increases extracellular 5-HT due to reuptake inhibition. Increased extracellular 5-HT can activate autoreceptors which may decrease serotonergic activity, thereby reducing the delta9-THC-induced hypothermia. Conversely, when fluoxetine is administered after delta9-THC, the reuptake block is thought to potentiate the already activated serotonergic system, hence potentiating the delta9-THC-induced hypothermia.
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PMID:Modulation of delta9-tetrahydrocannabinol-induced hypothermia by fluoxetine in the rat. 972 53

The purpose of this study was to prove the hypothesis that ET-1 production is increased in the splanchnic-hepato circulation during cardiopulmonary bypass (CPB) with or without hypothermia and this greatly affects hepatocellular function after surgery. Twelve Japanese white rabbits were used. In group I (n = 6), the rectal temperature was kept at 37.0 degrees C during CPB (90 min). In group II (n = 6), the rectal temperature was lowered to 26 degrees C during the first 30 minutes and then increased to 37 degrees C for the following 60 minutes. In group I, surface liver tissue blood flow (LBF) remained stable during CPB. While, in group II, LBF was significantly reduced to 66.9% of baseline values during hypothermic CPB, but it increased during the rewarming phase to 84.3% of the baseline value (p = 0.0070). At the end of CPB, portal ET-1 levels were increased in both groups, but they were significantly higher in group II (7.32 +/- 0.50 pg/ml and 9.29 +/- 0.61 pg/ml, respectively). Serum GOT, GPT, LDH and arterial ammonia levels were also higher in group II. Portal ET-1 levels had a significant positive correlation with those liver enzymes. Histopathological examination after CPB showed severe damage of the hepatic parenchyma in zone 3 associated with microvesicular fatty infiltration in group II.
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PMID:Increased portal endothelin-1 level is associated with the liver function after cardiopulmonary bypass in rabbits: influence of hypothermia on the damage. 984 52

We examined the long term effect of 3,4 methylenedioxymethamphetamine (MDMA, 10, 20 and 30 mg/kg, i.p.) on the cerebral 5-hydroxytryptamine (5-HT) and dopamine content in Swiss Webster mice. Three injections of MDMA (20 or 30 mg/kg, i.p.) given 3 h apart produced a marked depletion in the striatal content of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) 7 days later. None of the doses administered altered the concentration of 5-HT or its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in several brain areas. Pre-treatment with the dopamine uptake inhibitor GBR 12909 (10 mg/kg, i.p.), 30 min before each of the three MDMA (30 mg/kg, i.p.) injections, completely prevented the long term loss in the striatal catechol concentrations. However, GBR 12909 (10 mg/kg, i.p.) not only failed to prevent the acute effects induced by MDMA (30 mg/kg x 3, i.p.) on dopamine metabolism 30 min later, but in fact potentiated them. The 5-HT uptake inhibitor, fluoxetine (10 mg/kg, i. p.) failed to prevent both the acute and long term dopaminergic deficits. MDMA (30 mg/kg x 3) altered the body temperature of the mice biphasically, producing a rapid hyperthermia followed by prolonged hypothermia. In contrast, MDMA (20 mg/kg x 3) produced an initial hypothermia followed by hyperthermia. The present experiments therefore appear to rule out any direct relationship between the neurotoxic effects of MDMA and its acute effects on body temperature in mice. Fluoxetine administered 30 min before each MDMA (30 mg/kg) injection prevented these temperature changes, while GBR 12909 was without effect. This suggests that the neuroprotective effect of GBR 12909 against MDMA-induced neurotoxicity is not directly related to its ability to inhibit the MDMA-induced acute effects on dopamine metabolism or alter the MDMA-induced temperature change. The data illustrate major differences in the neurotoxic profile of MDMA in mice and rats.
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PMID:Effect of GBR 12909 and fluoxetine on the acute and long term changes induced by MDMA ('ecstasy') on the 5-HT and dopamine concentrations in mouse brain. 1107 72

Anxiety, platelet serotonin (5-HT) content and functions of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were measured in Sprague--Dawley (SD) and Fawn-Hooded (FH) rats, a strain with genetically impaired 5-HT storage and reuptake system and a putative model of depression and anxiety. In addition, the effects of 7 and 16 days treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine on 8-OH-DPAT-induced responses were studied. FH rats showed significantly higher anxiety in the social interaction test, and much lower platelet 5-HT content compared to SD rats. The efficacy of 8-OH-DPAT (15-120 microg/kg, i.v.) to induce lower lip retraction (an effect mediated by median raphe receptors) was increased in FH rats. In most FH but only a few SD rats a special neurological syndrome, clonic movement of the masseters and in-and-out movement of the eyeballs, was induced by 8-OH-DPAT, and this behaviour like other effects of 8-OH-DPAT, was completely blocked by pretreatment with the 5-HT(1A) receptor antagonist WAY-100635. In SD rats fluoxetine (10 mg/kg/day, i.p.) caused a moderate inhibition of 8-OH-DPAT-induced hypothermia, an effect mediated most likely by hypothalamic 5-HT(1A) receptors, (-19% and -40% after 7 and 16 days of fluoxetine, 24 h after the last injection, respectively). In FH rats fluoxetine caused a rapid and complete reduction in the 8-OH-DPAT-induced hypothermia (-65% and -91% after 7 and 16 days of fluoxetine, respectively). Fluoxetine caused no change in lower lip retraction but a reduction in the masseter-eyeball syndrome in both SD and FH rats. Our data provide evidence that in FH rats, median raphe 5-HT(1A) receptors are hypersensitive, and the hypothalamic 5-HT(1A) receptor desensitization, caused by SSRI antidepressants, is faster and more complete. These data support the notion that chronic treatment with SSRIs induces a desensitization of some 5-HT(1A) receptor populations, and impaired 5-HT storage and reuptake may accelerate this process.
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PMID:Rapid desensitization of 5-HT(1A) receptors in Fawn-Hooded rats after chronic fluoxetine treatment. 1122 8

Antidepressants produce various immunomodulatory effects, as well as an attenuation of the behavioral responses to immune challenges, such as lipopolysaccharide (LPS). To explore further the effects of antidepressants on neuroimmune interactions, rats were treated daily with either fluoxetine (Prozac) or saline for 5 weeks, and various behavioral, neuroendocrine, and immune functions were measured following administration of either LPS or saline. Chronic fluoxetine treatment significantly attenuated the anorexia and body weight loss, as well as the depletion of CRH-41 from the median eminence and the elevation in serum corticosterone levels induced by LPS. Chronic treatment with imipramine also attenuated LPS-induced adrenocortical activation. In rats and in mice, which normally display a biphasic body temperature response to LPS (initial hypothermia followed by hyperthermia), chronic treatment with fluoxetine completely abolished the hypothermic response and facilitated and strengthened the hyperthermic response. The effects of antidepressants on the responsiveness to LPS are probably not mediated by their effects on peripheral proinflammatory cytokine production, because LPS-induced expression of TNFalpha and IL-1beta mRNA in the spleen (assessed by semiquantitative in situ hybridization) was not altered following chronic treatment with either fluoxetine or imipramine. The effects of antidepressants on the acute phase response may have important clinical implications for the psychiatric and neuroendocrine disturbances that are commonly associated with various medical conditions.
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PMID:Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents. 1128 53

The effect of fluoxetine, a selective 5-HT reuptake inhibitor on the analgesic and hypothermic response of trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methane sulphonate (U-50,488H) and (+/-)-trans-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzo[b] thiophene-4-acetamide (PD 117302), kappa-opioid receptor agonists, was determined in female Sprague-Dawley rats using the tail-flick method and telethermometer, respectively. Intraperitoneal injections of U-50,488H (U50) and PD 117302 (PD117) produced a dose-dependent analgesic and hypothermic response. Fluoxetine (10 mg/kg, i.p.) by itself did not produce an analgesic response. The analgesic response to U50 (10, 20, and 40 mg/kg, i.p.) and PD117 (7.5, 15, and 22.5 mg/kg, i.p.) was potentiated by fluoxetine injected intraperitoneally 60 min prior to the injection of kappa-opioid agonists. Similarly, the hypothermic response of U50 (20 and 40 mg/kg, i.p.) and PD117 (7.5, 15, and 22.5 mg/kg, i.p.) was potentiated by fluoxetine. The results indicate that selective kappa-opioid receptor agonists-induced analgesia and hypothermia is potentiated by fluoxetine, suggesting the role of extracellular 5-HT in the kappa-opioid receptor-mediated analgesia and hypothermia.
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PMID:Potentiation of kappa-opioid receptor agonist-induced analgesia and hypothermia by fluoxetine. 1142 85


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