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热耐受性可减轻高温引起的工作记忆破坏:内源性阿片类物质起作用了吗?

Thermal tolerance reduces hyperthermia-induced disruption of working memory: a role for endogenous opiates?

作者信息

Mickley G A, Cobb B L

机构信息

Armstrong Laboratory, Radiofrequency Radiation Division (AL/OER), Brooks AFB, TX 78235-5324, USA.

出版信息

Physiol Behav. 1998 Mar;63(5):855-65. doi: 10.1016/s0031-9384(98)00010-9.

DOI:10.1016/s0031-9384(98)00010-9
PMID:9618009
Abstract

Previous reports indicate that microwave-induced hyperthermia can impair learning and memory. Here, we report that preexposure to a single 20-min period of hyperthermia can produce thermal tolerance and, thereby, attenuate future physiological and behavioral reactions to heating. Because endogenous opioids have been implicated in thermoregulation and reactions to microwave exposure, we also determined how opioid receptor antagonism might modulate these effects. In an initial experiment, rats were exposed daily, over 5 successive days, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. In animals exposed to microwaves, thermal tolerance was evidenced by declining rectal temperatures over time. Temperature reductions following microwave exposure were prominent after a single previous exposure. Therefore, in a second study, a single hyperthermic episode was used to induce thermal tolerance. On Day 1, rats were either exposed, over a 20-min period, to 600-MHz microwaves (at a whole-body specific absorption rate of 9.3 W/kg) or sham exposed. Just prior to radiation/sham-radiation treatment, rats received either saline or naltrexone (0.1 or 10 mg/kg, intraperitoneally (i.p.)). The following day (Day 2), rats were either microwave or sham exposed and tested on a task which measures the relative time subjects explore a familiar versus a novel stimulus object. Normothermic rats spend significantly more time in contact with new environmental components and less time with familiar objects. Brain (dura) and rectal temperatures were recorded on both days of the study. Microwave exposure produced a reliable hyperthermia which was significantly lower (on Day 2) in rats receiving repeated treatments (tolerant group). On the behavioral test, rats exposed only once to microwave-induced hyperthermia (nontolerant group) exhibited significantly different patterns of object discrimination than did tolerant or sham-exposed animals. Sham-exposed and tolerant animals showed a distinct preference for the new object whereas the nontolerant animals did not. Naltrexone (10 mg/kg) antagonized the hyperthermia-induced disruption of the object discrimination task (in nontolerant rats) and produced patterns of object exploration that were similar to those of sham-irradiated and thermal-tolerant rats, suggesting that endogenous opioids play a role in the organism's response to heating. Taken together, these data are consistent with the conclusions that 1) microwave-induced hyperthermia can cause a dose-dependent disruption of the normal discrimination between new and familiar objects, 2) physiological reactions to a single hyperthermic episode can produce a thermotolerance that expresses itself in both reduced levels of hyperthermia and attenuated behavioral disruptions following microwave exposure, and 3) opioid antagonism can partially reverse some of the behavioral effects of microwave-induced hyperthermia.

摘要

先前的报告表明,微波诱导的体温过高会损害学习和记忆能力。在此,我们报告,预先暴露于单次20分钟的体温过高状态可产生热耐受性,从而减弱未来对加热的生理和行为反应。由于内源性阿片类物质与体温调节及对微波暴露的反应有关,我们还确定了阿片受体拮抗剂如何调节这些效应。在最初的实验中,大鼠连续5天每天暴露于600兆赫的微波(全身比吸收率为9.3瓦/千克)或假暴露。在暴露于微波的动物中,随着时间的推移直肠温度下降证明了热耐受性。在单次先前暴露后,微波暴露后的体温降低很明显。因此,在第二项研究中,使用单次高温发作来诱导热耐受性。在第1天,大鼠在20分钟内暴露于600兆赫的微波(全身比吸收率为9.3瓦/千克)或假暴露。就在辐射/假辐射处理之前,大鼠接受生理盐水或纳曲酮(0.1或10毫克/千克,腹腔内注射)。第二天(第2天),大鼠要么接受微波暴露要么假暴露,并在一项测量受试者探索熟悉刺激物体与新刺激物体相对时间的任务中进行测试。体温正常的大鼠与新环境成分接触的时间明显更长,与熟悉物体接触的时间更短。在研究的两天中都记录了大脑(硬脑膜)和直肠温度。微波暴露产生了可靠的体温过高,在接受重复治疗的大鼠(耐受组)中(第2天)明显较低。在行为测试中,仅一次暴露于微波诱导的体温过高的大鼠(非耐受组)表现出与耐受或假暴露动物明显不同的物体辨别模式。假暴露和耐受的动物对新物体表现出明显的偏好,而非耐受的动物则没有。纳曲酮(10毫克/千克)拮抗了体温过高诱导的物体辨别任务的破坏(在非耐受大鼠中),并产生了与假照射和热耐受大鼠相似的物体探索模式,表明内源性阿片类物质在机体对加热的反应中起作用。综上所述,这些数据与以下结论一致:1)微波诱导的体温过高可导致对新物体和熟悉物体的正常辨别出现剂量依赖性破坏;2)对单次高温发作的生理反应可产生热耐受性,表现为微波暴露后体温过高水平降低和行为破坏减弱;3)阿片受体拮抗可部分逆转微波诱导的体温过高的一些行为效应。

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