The Persistent Neurotoxic Effects of Methamphetamine on Dopaminergic and Serotonergic Markers in Male and Female Rats.

Toxicology: open access Pub Date : 2016-01-01 Epub Date: 2016-09-06 DOI:10.4172/2476-2067.1000116
Lisa M McFadden, Paula L Vieira-Brock
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引用次数: 8

Abstract

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.

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甲基苯丙胺对雌雄大鼠多巴胺能和血清素能标记物的持续性神经毒性作用。
目的:甲基苯丙胺(冰毒)是一种高度成瘾性物质滥用在世界范围内的男性和女性。对雄性啮齿动物的临床前研究表明,大剂量暴露于甲基安非他明可导致大脑各区域持续的神经毒性后果。然而,很少有研究关注性在甲基安非他明暴露的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甲基苯丙胺(4次注射7.5 mg/kg)或生理盐水中。暴露于甲基苯丙胺的女性体温升高,因此男性和女性的体温升高情况相似。8 d后处死大鼠,观察纹状体、海马、额叶皮质和嗅球的神经化学变化。结果:结果显示,雄性和雌性暴露于甲基安非他明的大鼠纹状体多巴胺(DA)转运体(DAT)免疫反应性、海马5-羟色胺(5-HT)含量和5-羟色胺转运体(SERT)功能以及额叶皮层5-HT含量均有相似的下降。然而,与性别匹配的对照组相比,暴露于冰毒的雌性大鼠嗅球中5-HT含量的下降幅度更大,而暴露于冰毒的雄性大鼠与性别匹配的对照组没有显著差异。结论:这些发现表明,当暴露于冰毒的雄性和雌性大鼠之间保持相似的高温时,冰毒的神经毒性作用在某些大脑区域是相似的,但不是所有的大脑区域。
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The Persistent Neurotoxic Effects of Methamphetamine on Dopaminergic and Serotonergic Markers in Male and Female Rats.
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