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)

Hypothermic effects of d-Amphetamine, chlorpromazine, a variety of other phenothiazines, ET495 and haloperidol in rats at 4 degrees C were measured separately and in combination. All the drugs produced some hypothermia. Among the phenothiazines, degree of hypothermia induced was found to be correlated with relative effectiveness of the drug as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetadrugs as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetamine was greater than for either drug alone. Hypothermic effects of the combination CPZ with Amphetamine was potentiated by haloperidol but blocked by ET495. The evidence supports a model of neuronal feedback loops either within the central DA mesolimbic pathway or between the mesolimbic and nigrostriatal DA systems. The establishment of interdependency between antipsychotic and hypothermic effects of phenothiazines offers promise not only to a greater understanding of the mechanisms underlying these effects, but the possibility of an objective test for screening new materials for antipsychotic effectiveness.
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PMID:The possible role of dopamine in phenothiazine-induced hypothermia in rats: an application to DA hypothesis of schizophrenia. 1 69

The "thermoregulatory theory of hunger" posits that rats placed in a cold environment should increase the amount of food intake, while rats placed in a hot environment should decrease their food intake. d-Amphetamine causes hyperthermia among rats kept at warm ambient temperature, and results in hypothermia among animals kept in a cold environment. d-Amphetamine-caused-hyperthermia should therefore result in decreased eating behavior, and d-amphetamine-caused hypothermia should result in increased eating behavior. One must take into account the fact that d-amphetamine is an anorexic drug. The interaction between (a) ambient temperature, (b) body temperature and (c) food intake were tested on groups of rats injected with various doses of d-amphetamine (1.5-15 mg/kg) and placed in ambient temperatures ranging from 4-37 degrees C. No increase in food intake was revealed under any dosage or temperature condition. The decrease in food intake found with d-amphetamine treated animals could not be explained in the "thermoregulatory theory of hunger". Our data indicate that d-amphetamine anorexic effects and thermal effects are mediated by different mechanisms.
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PMID:Interaction effects of d-amphetamine treatment and ambient temperature on rat's food intake. 94 16

We used the reversibly binding D2 dopamine receptor radioligand [123I]IBZM (iodobenzamide) to test whether the endogenous neurotransmitter dopamine competes in vivo for radiotracer binding measured with single photon emission computed tomography (SPECT). In a series of nonhuman primate experiments (n = 27), the effects of temperature, amphetamine, haloperidol, and reserpine on brain uptake of [123I]IBZM were measured. Specific brain uptake of [123I]IBZM reached a peak by 100 min postinjection of radioligand and demonstrated a gradual, apparent "steady-state" washout over the next 2 hr. Brain uptake was temperature dependent, with rates of washout of specifically bound radioligand greater under normothermic conditions (26%/hr: core body temperature 35-37 degrees C) than under conditions of controlled hypothermia (11%/hr; 32-34 degrees C). Given the greater retention of radioactivity, low-temperature conditions were used in all other experiments. Administration of haloperidol (0.02 mg/kg IV) during the period of apparent steady state resulted in a dramatic increase in washout (60%/hr; p less than 0.0001), consistent with its potent D2 receptor antagonist properties. d-Amphetamine (1.0 mg/kg IV), which has negligible affinity for the D2 receptor but mediates the release of endogenous stores of dopamine, also enhanced washout (34%/hr; p less than 0.0005). Reserpine pretreatment at doses (1.0 mg/kg) sufficient to cause greater than 90% depletion of striatal dopamine levels blocked this amphetamine-enhanced washout (10%/hr; p less than 0.05). Reserpine did not block the increased washout induced by the direct-acting D2 receptor antagonist haloperidol. These results are consistent with the hypothesis that endogenous dopamine may effectively compete for radioligand binding in vivo in neuroreceptor imaging studies using PET and SPECT.
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PMID:Amphetamine-stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates. 153 75

GK 13 (N-[1-(2-benzo (b) thiophenyl)-cyclohexyl] piperidine), GBR 12783 (1-[2-(diphenylmethoxy)-ethyl] 4-(3-phenyl propenyl)-piperazine and dexamphetamine are three indirect catecholaminergic agonists, acting via different neurochemical mechanisms. We have compared their effects in rodents, in several behavioral tests. All three drugs increased locomotion. The stimulant locomotor effect of dexamphetamine was more easily antagonized by haloperidol than that of GBR 12783 and GK 13. Only dexamphetamine reversed reserpine-induced akinesia. This reversal was prevented by pretreatment with either GK 13 or GBR 12783. The three drugs reduced pentobarbital sleeping time in mice. They induced rotation ipsilateral to a unilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. The stereotypies induced by GK 13 and GBR 12783 were essentially limited to sniffing. Haloperidol-induced catalepsy was apparently more easily antagonized by dexamphetamine than by GK 13 or GBR 12783. GK 13 and GBR 12783 had no significant effects on body temperature. The three drugs displayed an anti-immobility effect in the "despair test". Dexamphetamine and GK 13 reversed the hypothermia induced by apomorphine (16 mg/kg), as well as reserpine-induced hypothermia and reserpine-induced ptosis. Dexamphetamine induced a dose-dependent anorectic effect, whereas GK 13 and GBR 12783 induced only a brief and partial anorexia. Similar observations were made on water intake. Pretreatment with either GBR 12783 or GK 13 did not affect the dexamphetamine-induced anorexia. Effects of the three drugs are discussed by reference to their known neurochemical properties on catecholaminergic transmission.
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PMID:Comparison of the effects of three indirect dopamine agonists, GK 13, GBR 12783 and dexamphetamine on behavioural tests involving central catecholaminergic transmissions. 197 95

Single doses of d-amphetamine, chlorpheniramine or diazepam were combined with ethanol under two conditions: (i) in drug-naive mice and (ii) in mice which had been given a single dose of ethanol 72 hr previously. Ethanol was administered orally at doses of 6.0, 3.0 or 1.5 g/kg; doses of d-amphetamine, chlorpheniramine or diazepam were given intraperitoneally. Three parameters were measured; changes in rectal temperature, forced motor coordination, as evaluated by rotarod performance and concentrations of ethanol in blood. d-Amphetamine and chlorpheniramine attenuated the hypothermia induced by ethanol but had no effect on the motor-impairing effect of ethanol. Hypothermia induced by diazepam was unaffected by ethanol, but the combination appeared to impair maximally rotarod performance. Concentrations of ethanol in blood did not differ between ethanol-naive mice and mice which had received the same dose of ethanol 72 hr previously. Changes in body temperature and intoxication have been attributed to central actions of ethanol; however, the differential results obtained from the interactions between these drugs suggest differing sensitivities of the various systems which are affected by ethanol.
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PMID:Drug interactions with ethanol. Effects on body temperature and motor impairment. 370 79

Methylphenidate is a central nervous system stimulant with a spectrum of action similar to the effects of d-amphetamine. d-Amphetamine-induced hypothermia is mediated via release of dopamine in the DA mesolimbic pathway. Methylphenidate causes hypothermia among rats kept at 4 degrees C, but d-amphetamine is twice as potent as methylphenidate. Dose-response relationship of methylphenidate thermal effects exhibits a U-shape curve. The hypothermic effects of 5-15 mg/kg methylphenidate are mediated by central dopaminergic neurons, as pretreatment with haloperidol inhibits these effects. The hypothermia produced by larger doses of methylphenidate is not blocked by pretreatment with haloperidol and hypothermia induced by d-amphetamine is blocked by pretreatment with haloperidol.
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PMID:A comparison of the hypothermic effects of methylphenidate and d-amphetamine. 723 82

Two reference substances were used in the present study. d-Amphetamine is a direct catecholamine-releasing agent which has a marked stimulant effect upon locomotor activity at low to moderate doses and induces stereotypy at higher doses. (+/-)8-Hydroxy-2-(di-n-propylamino)-tetraline [(+/-)8-OH-DPAT] is a selective 5-HT1A receptor agonist which produces a well-defined behavioral syndrome and a dose-dependent hypothermia. The first aim of this study was to validate that the d-amphetamine-induced activity monitored by telemetry correlated to that concomitantly measured in automated cages and complement these measures with an ethologically based direct observational technique. d-Amphetamine (2.5 and 5.0 micromol/kg s.c.) stimulated locomotion as assessed with radiotelemetry, in automatic cages and by observation. Accompanying these behavioral effects was a concurrent increase (assessed by radiotelemetry) in heart rate but not in blood pressure. The second part of this study examined the pharmacological effects of (+/-)8-OH-DPAT (0.09-6.1 micromol/kg s.c.) on behavior (observation and activity) and temperature and on the cardiovascular system. (+/-)8-OH-DPAT induced the classical serotonergic syndrome of lower lip retraction, forepaw treading, and flattened body posture (observation), and this was accompanied by a concomitant hypothermia (radiotelemetry). (+/-)8-OH-DPAT also induced a dose-dependent and significant decrease in heart rate for 50 min of the 1-h long observation period. This was not accompanied by an increase in blood pressure in spite of the increased activity as seen with all three methods. These results show that radiotelemetry can be used as a tool to measure activity, core temperature, and the cardiovascular parameters in animals that are less stressed than those that are restrained for similar more invasive measurements, and that this technique can be used in combination with others to produce a more complete ethogram of the animal's responses to pharmacological challenges.
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PMID:A pharmacological validation of radiotelemetry in conscious, freely moving rats. 1010 Apr 95