Inhibition of the dorsomedial hypothalamus, but not the medullary raphe pallidus, decreases hyperthermia and mortality from MDMA given in a warm environment.
Inhibition of the dorsomedial hypothalamus, but not the medullary raphe pallidus, decreases hyperthermia and mortality from MDMA given in a warm environment.
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DOI：
10.1002/prp2.31
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发表时间：
2014-04-01
影响因子：
2.6
通讯作者：
Rusyniak, Daniel E
中科院分区：
文献类型：
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作者：
Zaretsky, Dmitry V;Zaretskaia, Maria V;Durant, Pamela J;Rusyniak, Daniel E
3,4 - 亚甲基二氧基甲基苯丙胺（MDMA）在温暖环境中服用时引发危及生命的体温过高，其核心机制尚未得到充分阐释。一般认为，MDMA会改变正常的体温调节回路，导致通过肩胛间棕色脂肪组织（iBAT）产热增加，以及通过皮肤血管收缩散热减少。我们研究了背内侧下丘脑（DMH）和延髓中缝苍白核（mRPa）在介导MDMA引起的iBAT、尾部血流及运动效应方面的作用。给大鼠植入导向套管，分别靶向参与调节iBAT和皮肤血管床的DMH或mRPa脑区。对所有动物，通过手术植入的遥测发射器记录核心体温和活动情况；此外，还记录iBAT温度（通过遥测发射器）或尾动脉血流（通过尾动脉多普勒袖带）。将动物置于32°C的环境舱中，微量注射对照剂或γ - 氨基丁酸（GABA）激动剂蝇蕈醇（80皮摩尔），随后静脉注射生理盐水或MDMA（7.5毫克/千克）。为避免过度痛苦，选择41°C的核心体温作为死亡替代指标。抑制DMH而非mRPa可预防死亡，并减轻体温过高和活动增加的情况。抑制DMH或mRPa对iBAT温度升高或尾部血流减少均无影响。虽然MDMA会增加iBAT产热并通过皮肤血管收缩减少散热，但已知介导这些效应的体温调节脑区并未参与其中。相反，抑制DMH可降低活动量和体温这一发现表明，活动可能是MDMA诱发体温过高的一个关键中枢因素。
The central mechanisms through which 3,4-methylenedioxymethamphetamine (MDMA) mediates life-threatening hyperthermia when taken in a warm environment are not well described. It is assumed that MDMA alters normal thermoregulatory circuits resulting in increased heat production through interscapular brown adipose tissue (iBAT) and decreased heat dissipation through cutaneous vasoconstriction. We studied the role of the dorsomedial hypothalamus (DMH) and medullary raphe pallidus (mRPa) in mediating iBAT, tail blood flow, and locomotor effects produced by MDMA. Rats were instrumented with guide cannulas targeting either the DMH or the mRPa brain regions involved in regulating iBAT and cutaneous vascular beds. In all animals, core temperature and locomotion were recorded with surgically implanted telemetric transmitters; additionally, either iBAT temperature (via telemetric transmitter) or tail artery blood flow (via tail artery Doppler cuff) were also recorded. Animals were placed in an environmental chamber at 32°C and microinjected with either control or the gamma-aminobutyric acid (GABA) agonist muscimol (80 pmol) followed by an intravenous injection of saline or MDMA (7.5 mg kg−1). To prevent undue suffering, a core temperature of 41°C was chosen as the surrogate marker of mortality. Inhibition of the DMH, but not the mRPa, prevented mortality and attenuated hyperthermia and locomotion. Inhibition of either the DMH or the mRPa did not affect iBAT temperature increases or tail blood flow decreases. While MDMA increases iBAT thermogenesis and decreases heat dissipation through cutaneous vasoconstriction, thermoregulatory brain regions known to mediate these effects are not involved. Rather, the finding that inhibiting the DMH decreases both locomotion and body temperature suggests that locomotion may be a key central contributor to MDMA-evoked hyperthermia.