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多巴胺传递选择性阻断和刺激过程中运动激活与脑温变化之间的关系。

Relationships between locomotor activation and alterations in brain temperature during selective blockade and stimulation of dopamine transmission.

作者信息

Brown P L, Bae D, Kiyatkin E A

机构信息

Cellular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, DHHS, 333 Cassell Drive, Baltimore, MD 21224, USA.

出版信息

Neuroscience. 2007 Mar 2;145(1):335-43. doi: 10.1016/j.neuroscience.2006.11.028. Epub 2006 Dec 29.

Abstract

It is well known that the dopamine (DA) system plays an essential role in the organization and regulation of brain activational processes. Various environmental stimuli that induce locomotor activation also increase DA transmission, while DA antagonists decrease spontaneous locomotion. Our previous work supports close relationships between locomotor activation and brain and body temperature increases induced by salient environmental challenges or occurring during motivated behavior. While this correlation was also true for psychomotor stimulant drugs such as methamphetamine and MDMA, more complex relationships or even inverted correlations were found for other drugs that are known to increase DA transmission (i.e. heroin and cocaine). In the present study we examined brain, muscle and skin temperatures together with conventional locomotion during selective interruption of DA transmission induced by a mixture of D1 and D2 antagonists (SCH-23390 and eticlopride at 0.2 mg/kg, s.c.) and its selective activation by apomorphine (APO; 0.05 and 0.25 mg/kg, i.v.) in rats. While full DA receptor blockade decreased spontaneous locomotion, it significantly increased brain, muscle and skin temperatures, suggesting metabolic brain activation under conditions of vasodilatation (or weakening of normal vascular tone). In contrast, APO strongly decreased skin temperature but tended to decrease brain and muscle temperatures despite strong hyperlocomotion and stereotypy. The brain temperature response to APO was strongly dependent on basal brain temperature, with hypothermia at high basal temperatures and weak hyperthermia at low temperatures. While supporting the role of DA in locomotor activation, these data suggest more complex relationships between drug-induced alterations in DA transmission, behavioral activation and metabolic brain activation.

摘要

众所周知,多巴胺(DA)系统在大脑激活过程的组织和调节中起着至关重要的作用。各种诱导运动激活的环境刺激也会增加DA传递,而DA拮抗剂会减少自发运动。我们之前的研究支持运动激活与由显著环境挑战诱导或在动机行为期间发生的大脑和体温升高之间存在密切关系。虽然这种相关性对于诸如甲基苯丙胺和摇头丸等精神运动兴奋剂药物也成立,但对于其他已知会增加DA传递的药物(即海洛因和可卡因),则发现了更复杂的关系甚至反向相关性。在本研究中,我们在大鼠中通过D1和D2拮抗剂混合物(SCH - 23390和依替必利,0.2mg/kg,皮下注射)诱导DA传递的选择性中断及其通过阿扑吗啡(APO;0.05和0.25mg/kg,静脉注射)的选择性激活,同时检测大脑、肌肉和皮肤温度以及传统运动情况。虽然完全阻断DA受体会降低自发运动,但它会显著提高大脑、肌肉和皮肤温度,表明在血管舒张(或正常血管张力减弱)的情况下大脑代谢激活。相比之下,尽管APO会导致强烈的运动亢进和刻板行为,但它会强烈降低皮肤温度,并倾向于降低大脑和肌肉温度。大脑对APO的温度反应强烈依赖于基础脑温,在高基础温度下为体温过低,在低基础温度下为轻度体温过高。这些数据虽然支持DA在运动激活中的作用,但表明药物诱导的DA传递改变、行为激活和大脑代谢激活之间存在更复杂的关系。

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