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

The effects of different dopamine (DA) D2 receptor agonists and the DA D2 receptor antagonist, emonapride, on body temperature were studied in male mice. The aim of the study was to test whether DA D2 receptor agonists ranging from full agonists to agonists with low efficacy could be differentiated by means of their effect on body temperature. Talipexole induced a marked hypothermia (maximum decrease of 6.5 degrees C). Apomorphine, quinelorane, (+)-4-propyl-9-hydroxy-naphtoxazine((+)-PHNO), and (-)-N-n-propylnorapomorphine ((-)-NPA) induced a maximum hypothermia of 3.5-4.1 degrees C. Quinpirole and (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP) induced a less pronounced hypothermia (1.7 and 1.5 degrees C), and preclamol ((-)-3-PPP), terguride and 3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl)-(1))-butyl)-indole (EMD 23448) had no or only a slight effect. Emonapride induced significant hyperthermia at high doses. Apomorphine-, quinelorane- and talipexole-induced hypothermia was reversed by terguride and preclamol, whereas EMD 23448 partially reversed the apomorphine-induced hypothermia. The alpha 2-adrenoceptor antagonist, idazoxan, partly reversed the effect of talipexole. Quinpirole had no effect on the hypothermic effect of the above-mentioned agonists. Pretreatment with the catecholamine synthesis inhibitor, alpha-methyl-m-tyrosine, increased significantly the hypothermic response to quinpirole, whereas the effect of quinelorane was unchanged. It is suggested that the effect of DA D2 agonists on body temperature in mice can be used to differentiate between agonists with different efficacies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects on body temperature in mice differentiate between dopamine D2 receptor agonists with high and low efficacies. 135 51

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

The ability of neuroleptics to induce dopamine D2 receptor supersensitivity has been linked to the onset of tardive dyskinesia, the major side-effect of these drugs. Brain iron metabolism has been shown to be involved in the regulation of dopamine D2 receptors. We now examined the effect of chronic treatment with FeCl2 on chlorpromazine-induced D2 receptor supersensitivity. The results show that FeCl2 (5 mg/kg per day for 21 days) given to rats treated with chlorpromazine (10 mg/kg per day, for 21 days) prevented the onset of supersensitive biochemical and behavioral (apomorphine) expressions of DA D2 receptor. Inclusion of iron did not affect the chlorpromazine-induced sedation or hypothermia. Moreover, the combined chronic iron-chlorpromazine treatment produced the same net effects as chronic chlorpromazine on striatal amounts of dopamine, DOPAC (dihydroxyphenylacetic acid) and HVA (homovanillic acid). Chlorpromazine medication caused a decrease in liver non-haem iron levels (40%) but not in brain iron. The effect of the neuroleptic drug on iron stores and the involvement of iron in the neuroleptic-induced dopamine supersensitivity suggest that mobilization of iron from the periphery into the brain may play an important role in the mechanism of action of the neuroleptics.
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PMID:Prevention of neuroleptic-induced dopamine D2 receptor supersensitivity by chronic iron salt treatment. 168 31

It has been demonstrated that nutritional iron-deficiency induced in rats results in the reduction of DA D2 receptor binding sites, leading to down-regulation of dopaminergic activity similar to that observed in neuroleptic-treated animals. The following observations are common to both conditions: (a) Decreased behavioural response to pre- and post-synaptically DA and serotonin acting drugs, amphetamine, apomorphine and 5-methoxy-N,N-dimethyltryptamine. (b) Inhibition of amphetamine or apomorphine induced hypothermia in rats kept at an ambient temperature of 4 degrees C. (c) Increased sleeping time to phenobarbitone which cannot be attributed to the rate of drug metabolism (5,38). (d) Upregulation of prolactin binding sites in the liver as a result of increased serum prolactin. Additionally, nutritional iron-deficiency lowers brain iron and interferes with protein synthesis in this organ, which could explain the reduction of DA D2 receptor number and function. Given the fact that the highest brain concentrations of iron are found in dopaminergic structures (see 42 for review), and the essential role of intact dopaminergic systems to attentional and learning processes (15b,30), the resultant behavioural changes due to the reduction of dopaminergic activity in iron-deficient animals may go some way to explain the adverse effects on cognition, behavioural patterns, learning and attention, event-related potentials (ERPs) and EEG changes reported in iron-deficient children (19-28,30).
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PMID:Brain iron and dopamine receptor function. 613 53

In mice pretreated intracerebroventricularly (i.c.v.) with 6-hydroxydopamine (6OHDA) (50 micrograms per mouse), as soon as the hypothermia elicited by the neurotoxin had vanished (3 hr), the hypothermic effect induced by the direct D2 dopamine receptor agonist RU 24926 (1 mg/kg, s.c.), was almost completely suppressed. This reduction in hypothermic effect was observed more than 1 month after the 6OHDA injection. On the 3rd day after 6OHDA injection, this reduction was observed for all tested doses of RU 24926 (0.25-2 mg/kg). It was prevented when an i.p. administration of the norepinephrine uptake inhibitor desipramine (20 mg/kg) was performed 30 min before the 6OHDA i.c.v. injection. It was not modified when an i.p. administration of the dopamine uptake inhibitor GBR 12783 (20 mg/kg) was performed 30 min before the 6OHDA i.c.v. injection. The 6OHDA i.c.v. injection modified significantly neither the dopamine nor the serotonin hypothalamic contents. On the contrary it resulted in a marked decrease (-73%) of the norepinephrine hypothalamic content, which was unchanged by the administration of GBR 12783 (20 mg/kg, i.p.) 30 min before 6OHDA, but completely prevented by desipramine (20 mg/kg, i.p.) 30 min before 6OHDA i.c.v. injection. It is concluded that the hypothermic effect resulting from the stimulation of D2 dopamine receptors involves a central norepinephrine transmission, which is very rapidly altered after 6OHDA administration.
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PMID:Rapid and long lasting reduction of the hypothermic effect of a D2 dopamine agonist after an intracerebroventricular injection of 6-hydroxydopamine. 762 58

The direct D2 dopamine receptor agonist RU 24926, administered subcutaneously to mice, elicited, starting at the dose of 0.125 mg/kg, a dose dependent analgesic effect, assessed as the jump latency from a hot plate (55 degrees C). The analgesic effect induced by 0.25 mg/kg RU 24926 was dose dependently antagonized by the preferential D2 dopamine receptor antagonist haloperidol (ID50 = 15.1 +/- 3.3 micrograms/kg sc) as well as by the opioid receptor antagonist naloxone (ID50 = 0.59 +/- 0.17 mg/kg sc). The reversion of RU 24926-induced analgesia by naloxone was not accompanied by a reversion of hypothermia. Semi-chronic administration of RU 24926 (2.5 mg/kg, sc, 3 times a day for 3 days) completely desensitized to the analgesic effect induced by a 0.25 mg/kg test dose of RU 24926 and partially reduced the analgesic effect of low doses of morphine (0.5, 1, 1.5 mg/kg). Conversely, semi-chronic administration of morphine (32 mg/kg sc, twice daily for 4 days) completely desensitized the analgesic effect induced by a 2 mg/kg test dose of morphine and partially reduced the analgesic effect of RU 24926 (0.25, 0.5 and 1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analgesic effect of the direct D2 dopamine receptor agonist RU 24926 and cross tolerance with morphine. 762 27

Remoxipride and its active metabolites, the phenolic compounds FLA797(-) and FLA908(-) and the catecholic NCQ436(-) and haloperidol, were examined for their ability to block hypothermia in the rat induced by dopamine (DA) D2 receptor stimulation. In addition, plasma levels of remoxipride and its active metabolites were measured using HPLC methods. Remoxipride (1 mumol/kg), given 30 or 15 min prior to, or 5 and 15 min after, the DA agonists, blocked the hypothermia induced by the DA D2 receptor agonists quinpirole (0.25 mg/kg s.c.) and pergolide (0.1 mg/kg s.c.). Administration of remoxipride by the i.v. or s.c. routes was more effective than by the i.p. route. FLA797(-), FLA908(-), and haloperidol were more effective than remoxipride in preventing the hypothermia caused by quinpirole, while NCQ436(-) was less effective than remoxipride. The variation in time of remoxipride's action and effectiveness in blocking the induced hypothermia followed the variations in plasma concentrations. The plasma concentrations of the active metabolites were below the limit of determination (< 2 nmol/l). Based on estimation of free brain concentrations at effective dose levels together with in vitro affinities for the DA D2 receptor it was concluded that the metabolites FLA797(-), FLA908(-), and NCQ436(-) do not appear to contribute to the antagonism of DA D2 mediated neurotransmission following a low remoxipride dose (1 mumol/kg).
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PMID:Dopamine D2 blocking activity and plasma concentrations of remoxipride and its main metabolites in the rat. 821 58

The dopamine (DA) D2-like family of receptors is comprised of three subtypes, the D2, D3, and D4 receptors. It has been suggested that the potency of DA receptor agonists to produce hypothermia and hypolocomotion in rodents correlates more strongly with the in vitro affinity for, or potency (mitogenesis test) at the D3 than at the D2 subtype. However, it has recently been reported that when tested in DA D3 receptor knock-out mice, several DA D2/D3 receptor agonists (7-OH-DPAT, PD 128907 and quinelorane) induced levels of hypothermia and decreases of locomotor activity similar to those obtained in control (wild-type) mice. These results do not argue in favour of an implication of DA D3 receptors in these in vivo effects. In order to investigate whether the DA D2 receptor is the subtype that mediates hypothermia and hypolocomotion produced by DA D2/D3 receptor agonists, we tested the effects of ip administration of the DA D2/D3 receptor agonists 7-OH-DPAT and PD 128907, on core temperature and locomotor activity in DA D2 receptor knock-out mice (homozygotes: D2(-/-) and heterozygotes: D2(+/-)), and in wild-type (D2(+/+)) mice. 7-OH-DPAT (0.1-3 mg/kg) and PD 128907 (1-10 mg/kg) induced hypothermia and decreased locomotion in D2(+/+) mice, but had no effects in D2(-/-) mice; the magnitude of the hypothermic and locomotor-reducing effects of these two agonists in D2(+/+) mutants was approximately half that of D2(+/+) mice. During the first 10 min in the activity chambers, the level of spontaneous locomotor activity of D2(-/-) individuals was almost 50% below that of D2(+/+) mice; basal locomotor activity of D2(+/-) mice was between that of D2(-/-) and D2(+/+) individuals. Neither type of mutant showed spontaneous catalepsy or deficits in forelimb muscle strength (grip-strength test). These results show that the presence of DA D2 receptors is necessary for the expression of the locomotor- and core temperature-decreasing effects of DA D2/D3 receptor agonists such as 7-OH-DPAT and PD 128907.
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PMID:Dopamine D2 receptor knock-out mice are insensitive to the hypolocomotor and hypothermic effects of dopamine D2/D3 receptor agonists. 1047 Oct 93

The atypical antipsychotic olanzapine (2.5-20 mg/kg) produced hypothermia in rats. The decrease in rectal temperature caused by olanzapine (2.5-20 mg/kg) was blocked by the selective dopamine D2 receptor antagonist pimozide (0.5 and 1 mg/kg) but not by the dopamine D1 receptor antagonist SCH 23390 (0.5 and 1 mg/kg). The dopamine D1/D2 receptor agonist apomorphine (3 mg/kg) and the selective dopamine D2 receptor agonist talipexole (0.5 mg/kg) produced hypothermia in rats. Olanzapine (10 and 20 mg/kg) significantly blocked hypothermia produced by both apomorphine and talipexole while the lower doses (2.5 and 5 mg/kg) of olanzapine failed to block it. The present results demonstrate that olanzapine behaves as a partial agonist at brain DA D2 receptor populations involved in thermoregulation in the rat.
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PMID:Antagonism by pimozide of olanzapine-induced hypothermia. 1052 Jul 26

Cannabinoids produce analgesia, hypomotility, catalepsy, cognitive deficits and positive reinforcement. Moreover, Delta(9)-tetrahydrocannabinol (9-THC) and synthetic cannabinoids stimulate dopaminergic neurons and increase dopamine release in different brain areas. In order to clarify the role of endogenously released dopamine in the hypothermic response to cannabinoids, the effect of D(1) and D(2) dopamine receptor agonists and antagonists on Delta(9)-THC-induced hypothermia was studied in rats. Delta(9)-THC (2.5 and 5 mg/kg intraperitoneally [IP]) decreased body temperature in a dose-related manner. This effect was antagonized not only as expected by the CB(1) cannabinoid receptor antagonist SR 141716A (0.5 mg/kg, IP) but also, unexpectedly, by the dopaminergic D(2) receptor antagonists S(-)-sulpiride (5 and 10 mg/kg, IP) and S(-)-raclopride (1 and 3 mg/kg, IP). Conversely, the hypothermic effect of Delta(9)-tetrahydrocannabinol was potentiated by the D(2) dopamine receptor agonists (-)-quinpirole (0.025 and 0.500 mg/kg, SC) and (+)-bromocriptine (0.5 and 1 mg/kg, IP). In contrast, the Delta(9)-THC-induced hypothermic effect was not modified by either by the D(1) dopamine agonist SKF 38393 (10 mg/kg SC) or by the D(1) dopamine antagonist SCH 23390 (0.5 mg/kg SC). These results suggest that the D(2) dopamine receptors have a permissive role in the hypothermic action of cannabinoids.
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PMID:Permissive role of dopamine D(2) receptors in the hypothermia induced by delta(9)-tetrahydrocannabinol in rats. 1083 59


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