甲基苯丙胺对雄性和雌性大鼠多巴胺能和5-羟色胺能标志物的持续神经毒性作用
The Persistent Neurotoxic Effects of Methamphetamine on Dopaminergic and Serotonergic Markers in Male and Female Rats.
作者信息
McFadden Lisa M, Vieira-Brock Paula L
机构信息
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, SD 57069, USA.
出版信息
Toxicol Open Access. 2016;2(2). doi: 10.4172/2476-2067.1000116. Epub 2016 Sep 6.
OBJECTIVE
Methamphetamine (METH) is a highly addictive substance abused world-wide in both males and females. Preclinical studies in male rodents suggest that large-dose exposure to METH can lead to persistent neurotoxic consequences to various brain regions. However, little research has focused on the potential role of sex in the neurotoxic consequences of METH exposure.
METHODS
The current study exposed male and female rats to large-doses of METH (4 injections of 7.5 mg/kg) or saline. Hyperthermia was promoted in the females exposed to METH such that similar hyperthermia occurred in males and females. Rats were sacrificed 8 d later and neurochemical changes were assessed in the striatum, hippocampus, frontal cortex and olfactory bulbs.
RESULTS
Results revealed that male and female rats exposed to METH had similar decreases in dopamine (DA) transporter (DAT) immunoreactivity in the striatum, serotonin (5-HT) content and 5-HT transporter (SERT) function in the hippocampus, and 5-HT content in the frontal cortex. However, female rats exposed to METH had greater decreases in 5-HT content in the olfactory bulbs compared to sex-matched controls while male rats exposed to METH did not significantly differ from sex-matched controls.
CONCLUSIONS
These findings suggest that when similar hyperthermia is maintained between male and female rats exposed to METH, the neurotoxic effects of METH were similar in some, but not all brain regions.
目的
甲基苯丙胺（METH）是一种在全球范围内被男性和女性滥用的高度成瘾性物质。对雄性啮齿动物的临床前研究表明，大剂量接触METH会对各个脑区产生持续的神经毒性后果。然而，很少有研究关注性别在METH暴露所致神经毒性后果中的潜在作用。
方法
本研究将雄性和雌性大鼠暴露于大剂量的METH（4次注射，每次7.5mg/kg）或生理盐水中。对暴露于METH的雌性大鼠进行升温处理，以使雄性和雌性大鼠出现相似的体温过高情况。8天后处死大鼠，并评估纹状体、海马体、额叶皮质和嗅球中的神经化学变化。
结果
结果显示，暴露于METH的雄性和雌性大鼠在纹状体中的多巴胺（DA）转运体（DAT）免疫反应性、海马体中的5-羟色胺（5-HT）含量和5-HT转运体（SERT）功能以及额叶皮质中的5-HT含量均有相似程度的下降。然而，与性别匹配的对照组相比，暴露于METH的雌性大鼠嗅球中的5-HT含量下降幅度更大，而暴露于METH的雄性大鼠与性别匹配的对照组相比无显著差异。
结论
这些发现表明，当暴露于METH的雄性和雌性大鼠维持相似的体温过高时，METH的神经毒性作用在一些但并非所有脑区中是相似的。
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