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

Neurotensin enhances some of the behavioral effects of alcohol including motor impairment, narcosis, hypothermia and also interacts with some of the physiological actions of angiotensin (ANG) II including aldosterone release and increased blood pressure. ANG II injections also produce a dose-dependent antagonist reversible reduction in alcohol drinking. The present study is the first to examine the interaction between neurotensin and angiotensin in the behavioral context of oral alcohol self-administration. Adult male Wistar rats acquired alcohol drinking (6% w/v) using the limited access procedure which makes alcohol available for 40 min every day. When intake stabilized ANG II (400 micrograms/kg per day) or vehicle were administered subcutaneously (SC) just prior to alcohol availability but only the group receiving ANG II showed a marked reduction in alcohol intake. Following this the groups were pretreated sc with either vehicle or ascending doses of neurotensin (5, 10, 20 micrograms/kg) followed by either ANG II or vehicle. Control groups received either two vehicle injections or vehicle and neurotensin injection. Neurotensin alone did not affect alcohol intake at any of the doses tested but did attenuate, in a dose-dependent fashion, the reduction in alcohol intake produced by ANG II. These results demonstrate neurotensin's ability to alter the behavioral effect of ANG II on alcohol intake.
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PMID:Neurotensin attenuates the reduction in alcohol drinking produced by angiotensin II. 872 49

Neurotensin, an endogenous peptide widely distributed throughout the brain, fulfils neurotransmitter criteria. When administered centrally, neurotensin induces various effects and modulates the activity of the mesolimbic dopamine system. It antagonizes the behavioural action of dopamine in a manner similar, but not identical, to antipsychotic drugs. Neurotensin is even considered to be an endogenous neuroleptic. In fact, microinjection of neurotensin elicits different effects depending on both the dose and the cerebral structures into which the injection is made. Our work on the development of orally-active neurotensin antagonists has led to the identification of SR 48692, the first non-peptide antagonist of the neurotensin receptor, and some analogues. This small molecule reveals a surprising neuropharmacological profile. It antagonizes turning behaviour induced in mice and rats (after striatal or ventral tegmental area administration of neurotensin, respectively), hypolocomotion induced by intracerebroventricular injection of neurotensin in rats, and reverses the inhibitory effect of neurotensin (nucleus accumbens injection) on amphetamine-induced hyperlocomotion in rats. However, SR 48692 cannot reverse either dopamine release in the nucleus accumbens evoked by neurotensin injection in ventral tegmental area, or hypothermia and analgesia induced by intracerebroventricular injection of neurotensin. As direct and indirect dopamine agonists have been reported to promote neurotensin release in the cortex, behavioural studies were performed using injection of apomorphine. In these experiments, SR 48692 inhibited only turning and yawning. It did not antagonize other apomorphine-dependent effects such as climbing, hypothermia, hypo- or hyperlocomotion, penile erection and stereotypies. All together, these data raise the question of the existence of neurotensin receptor subtypes and confirm that the nature of neurotensin and dopamine interactions depends on the brain structures considered.
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PMID:Neuropharmacological profile of non-peptide neurotensin antagonists. 880 71

The endogenous tridecapeptide neurotensin exerts a wide range of behavioral, electrophysiological and neurochemical effects when administered directly into the brain. These effects are thought to result from the activation of distinct populations of neurotensin receptors distributed throughout the central nervous system. We have mapped the sites of functional change in the rat brain associated with the central administration of neurotensin using the induction of the nuclear protein products of the immediate early genes c-fos and zif268 as markers of cellular activation. The administration of neurotensin into the lateral ventricle of rats produced an increase in the number of nuclei positive for Fos and Zif268 immunoreactivity in the central and basolateral nuclei of the amygdala and the paraventricular and supraoptic nuclei of the hypothalamus. Neurotensin also produced an increase in serum corticosterone concentration and decrease in body temperature. The intraperitoneal administration of SR48692, a non-peptide neurotensin receptor antagonist, blocked the neurotensin-induced corticosterone secretion and significantly reduced the number of neurotensin-induced Fos-positive and Zif268-positive neurons in the amygdaloid complex. A significant positive correlation was found between the number of Fos-positive nuclei in the central or basolateral nucleus of the amygdala and the serum corticosterone concentration. A significant positive correlation was also found between the number of Zif-positive cells in the paraventricular nucleus of the hypothalamus and change in body temperature following treatment. Our findings indicate that the central role of neurotensin in increasing serum corticosterone involves the induction of Fos in the central and basolateral nuclei of the amygdala. In contrast, the neurotensin-induced hypothermia, which was unaffected by pretreatment with SR48692, involves Zif induction in the paraventricular nucleus of the hypothalamus. These data support further the existence of central neurotensin receptor subtypes which may regulate distinct immediate early genes.
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PMID:Neurotensin induces Fos and Zif268 expression in limbic nuclei of the rat brain. 893 47

Neurotensin (NT), a tridecapeptide, is a neurotransmitter that elicits potent effects including hypothermia and antinociception in mice and rats. To date, there are two types of the neurotensin receptor (NTR) that have been molecularly cloned from the rat. However, several lines of evidence suggest the presence of additional NTR subtypes. We have identified a NT analog of the NT(8-13) fragment, NT27, that selectively causes only the hypothermic response in vivo, when microinjected into the periaqueductal gray (PAG) of rats. A dose of 18 nmol of NT or NT27 caused a body temperature lowering of 1.8 and 1.2 degrees C, respectively. This same dose of NT or NT27 yielded a hotplate maximum physiological effect of 75% and 25%, respectively. Interestingly, despite its high KD (620 nM) at the cloned NTR-1, NT27-I (the iodinated form of NT27) exerted a potent hypothermic effect even at a very low dose (0.6 nmol). Equally intriguing, was that NT24, a sterioisomer of NT27, with a much higher affinity (KD=0. 5 nM) at NTR-1, did not selectively induce hypothermia in mice, but did selectively induce hypothermia in rats.
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PMID:Evidence for additional neurotensin receptor subtypes: neurotensin analogs that distinguish between neurotensin-mediated hypothermia and antinociception. 959 20

Neurotensin (NT) is a neuropeptide neurotransmitter in the central nervous system. It has been implicated in the therapeutic and in the adverse effects of neuroleptics. Activity of NT in brain can only be shown by direct injection of the peptide into that organ. However, we have developed a novel analog of NT(8-13), NT69L, which is active upon intraperitoneal (i.p.) injection. Like atypical neuroleptics, NT69L blocked the climbing behavior in rats, but not the licking and sniffing behaviors of a high dose (600 microgram/kg) of the non-selective dopamine agonist apomorphine. Its blockade of climbing was very potent with an ED(50) (effective dose at 50% of maximum) of 16 microgram/kg. Both apomorphine and NT69L caused a long-lasting hypothermia, which was greater with the peptide but not synergistic in combination with apomorphine. The ED(50) of NT69L for hypothermia was 390 microgram/kg. NT69L (up to 5 mg/kg i.p.) did not produce catalepsy. However, when given before haloperidol, NT69L, but not clozapine, completely prevented catalepsy. When given after haloperidol, NT69L, but not clozapine, reversed haloperidol's cataleptic effects with an ED(50) of 260 microg/kg. There was no significant difference between the ED(50)s for hypothermia and anticataleptic effects of NT69L. However, the ED(50) for blocking the effects of apomorphine was significantly lower than the other two. These data suggest that NT69L may have neuroleptic properties in humans and may be useful in the treatment of extrapyramidal side effects caused by typical neuroleptics such as haloperidol.
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PMID:Effects of a novel neurotensin peptide analog given extracranially on CNS behaviors mediated by apomorphine and haloperidol. 1067 10

Neurotensin (NT) is a tridecapeptide neurotransmitter in the central nervous system. It has been implicated in the therapeutic effects of neuroleptics. Central activity of NT can only be demonstrated by direct injection into the brain, since it is readily degraded by peptidases in the periphery. We have developed many NT(8-13) analogs that are resistant to peptidase degradation and can cross the blood-brain barrier (BBB). In this study, we report on one of these analogs, NT77L. NT77L induced hypothermia (ED(50)=6.5 mg/kg, i.p.) but induced analgesia only at the highest dose examined (20 mg/kg, i.p.). Like the atypical neuroleptic clozapine, NT77L blocked the climbing behavior in rats induced by the dopamine agonist apomorphine (600 microg/kg) with an ED(50) of 5.6 mg/kg (i.p.), without affecting the licking and the sniffing behaviors. By itself NT77L did not cause catalepsy, but it moderately reversed haloperidol-induced catalepsy with an ED(50) of 6.0 mg/kg (i.p.). Haloperidol alone did not lower body temperature, but it potentiated the body temperature lowering effect of NT77L. In studies using in vivo microdialysis NT77L showed similar effects on dopamine turnover to those of clozapine, and significantly different from those of haloperidol in the striatum. In the prefrontal cortex, NT77L significantly increased serotonergic transmission as evidenced by increased 5-hydroxyindole acetic acid:5-hydroxytryptamine (5-HIAA:5-HT) ratio. Thus, NT77L selectively caused hypothermia, over antinociception, while exhibiting atypical neuroleptic-like effects.
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PMID:Neurotensin analog selective for hypothermia over antinociception and exhibiting atypical neuroleptic-like properties. 1168 57

Neurotensin (NT) produces behavioral and physiological effects, including analgesia and hypotheria, when administered into the CNS. Fischer and Lewis rats exhibit differential behavioral responses to central NT receptor activation. To further characterize these differences, we assessed central NT-induced analgesia and hypothermia in independent groups of rats from each strain. Fischer and Lewis rats showed a similar dose-orderly analgesic response in a hot-plate test. Such an isosensitivity was not observed for NT-induced hypothermia. Although NT produced a dose-orderly decrease in mean rectal temperature in both strains, the magnitude of the hypothermic response was significantly smaller in Fischer than in Lewis rats. These findings provide further evidence of genetic differences in central neurotensinergeric neurotransmission in these two strains.
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PMID:Differential sensitivity to neurotensin-induced hypothermia, but not analgesia, in Fischer and Lewis rats. 1461 90

Neurotensin (NT) is a neuropeptide that induces a wide range of biological activities including hypothermia and analgesia. Such effects are mediated by the NT receptors Ntsr1, Ntsr2 and Ntsr3, although the involvement of each receptor in specific NT functions remains unknown. To address nociceptive function in vivo, we generated both Ntsr1-deficient and Ntsr2-deficient mice. In addition, histochemical analyses of both Ntsr1 and Ntsr2 mRNAs were performed in the mouse brain regions involved in NT-related nociception. The expression of Ntsr2 mRNA was greater than that of Ntsr1 in the periaqueductal gray (PAG) and the rostral ventral medulla (RVM). The mutant and control mice were subjected to the examination of thermal nociception, and in the hot plate test, a significant alteration in jump latency was observed in Ntsr2-deficient mice compared to Ntsr1-deficient or wild-type control mice. Latencies of tail flick and hind paw licking of the mutant mice were not affected compared to control mice. These results suggest that Ntsr2 has an important role in thermal nociception compared to Ntsr1, and that these mutant mice may represent a useful tool for the development of analgesic drugs.
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PMID:Comparison of mice deficient in the high- or low-affinity neurotensin receptors, Ntsr1 or Ntsr2, reveals a novel function for Ntsr2 in thermal nociception. 1472 75

Neurotensin (NT) is a tridecapeptide found in the nervous system, as well as elsewhere in the body. It has anatomic and functional relationships to dopaminergic neurons in brain. NT has been implicated in the actions of antipsychotic drugs and psychostimulants, and animal studies suggest that neurotensin directly injected into brain has reinforcing effects. Previously, we showed that one of our brain-penetrating analogs of neurotensin, NT69L (N-methyl-L-Arg, L-Lys, L-Pro, L-neo-Trp, L-tert-Leu, L-Leu), has many pharmacological effects in rats including antinociception, hypothermia, and blockade of the hyperactivity caused by psychostimulants (cocaine, D-amphetamine, and nicotine). Since these studies in rats suggest that this compound may have clinical use in humans, we were interested to know what effects NT69L had in primates. NT69L caused a potent antinociceptive effect against capsaicin (0.1 mg)-induced allodynia in 46 degrees C water in rhesus monkeys, inducing 40% of the maximal possible effect at an intravenous dosage of 0.03 mg/kg; its hypotensive effects precluded evaluation of higher dosages. Core temperature measured by rectal probe was modestly reduced at 0.01 and 0.03 mg/kg. In an intravenous self-administration procedure, NT69L was without reinforcing effects at any dose, including those that caused other pharmacological effects, and did not alter cocaine-maintained behavior when administered as a pretreatment.
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PMID:Antinociceptive, hypothermic, hypotensive, and reinforcing effects of a novel neurotensin receptor agonist, NT69L, in rhesus monkeys. 1568 Jan 87

Neurotensin is a linear tridecapeptide that elicits a variety of physiological responses in the brain, including hypothermia and antinociception, and reduced levels have been linked to schizophrenia. Previously in our laboratory we developed a truncated neurotensin derivative, KK13. This hexapeptide exhibited key pharmacokinetic and behavioural characteristics of an antipsychotic and elicited central effects after oral administration. To examine the potential mechanism(s) of uptake, a radioactive analogue of KK13 (*KK13) was synthesized, characterized, and evaluated in the Caco-2 cell model of the human intestinal epithelium. Results suggested that uptake of *KK13 was a time-dependent passive process. A general linear trend in uptake was demonstrated over the concentration range (10 microM-1 m M) tested, and uptake was neither pH- nor sodium-dependent. Finally, after 60 min, intact *KK13 was identified associated with the cell components, providing further evidence for uptake and stability of the peptide.
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PMID:Cellular uptake of a radiolabelled analogue of neurotensin in the Caco-2 cell model. 1580 88


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