Stress-induced neural activation is altered during early withdrawal from chronic methamphetamine
Stress-induced neural activation is altered during early withdrawal from chronic methamphetamine
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DOI：
10.1016/j.bbr.2019.03.034
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发表时间：
2019-07-02
影响因子：
2.7
通讯作者：
Zuloaga, Damian G.
中科院分区：
文献类型：
--
作者：
Jacobskind, Jason S.;Rosinger, Zachary J.;Zuloaga, Damian G.
长期使用甲基苯丙胺（MA）可导致戒断期间抑郁和焦虑症状增加。关于重复MA后可能与这些行为扰动相关的特定大脑区域的改变，我们知之甚少。此外，据报道，MA会招募和激活大脑中的小胶质细胞，这可能会加剧与压力相关的行为变化。在本研究中，雄性和雌性小鼠注射MA（5 mg/kg）或生理盐水，每天一次，持续10天，并在早期撤退期间评估立即早期基因（c-Fos）对强迫游泳应激源的反应的改变。在末次给药后48小时，雄性和雌性小鼠的强迫游泳试验中，长期MA暴露增加了漂浮时间，减少了游泳时间，表明抑郁样行为增加。此外，评估筑巢，一个措施的痛苦或绝望的行为，揭示了性别特异性的影响，只有MA处理的女性表现出损害。在中央杏仁核，CA 3海马区，前额叶皮层，和床核的终纹（BST）的c-Fos反应，以强迫游泳减弱事先MA曝光。在BST中，这种衰减仅发生在男性中。无论是小胶质细胞或激活的小胶质细胞的总数被改变慢性MA暴露在检查的区域。初步研究结果表明，慢性MA暴露减弱了选定的应激相关脑区的激活，这是一种可能导致情绪相关行为改变的失调。
Chronic methamphetamine (MA) use can lead to increased symptoms of depression and anxiety during abstinence. Less is known about the specific brain regions that are altered following repeated MA that may be associated with these behavioral perturbations. Furthermore, MA has been reported to recruit and activate microglia in the brain, which may exacerbate stress-associated behavioral changes. In the present study, male and female mice were injected with MA (5 mg/kg) or saline once daily for 10 days, and during early withdrawal were assessed for alterations in immediate early gene (c-Fos) responses to a forced swim stressor. Chronic MA exposure increased floating and decreased swim time in the forced swim test in male and female mice tested 48 h after the final dose, indicating elevated depressive-like behavior. Furthermore, assessment of nest building, a measure of distress or despair-like behavior, revealed a sex-specific effect with only MA-treated females showing impairments. The c-Fos response to forced swim was attenuated by prior MA exposure in the central amygdala, CA3 hippocampal region, prefrontal cortex, and bed nucleus of the stria terminalis (BST). In the BST this attenuation occurred only in males. Neither the total number of microglia or activated microglia were altered by chronic MA exposure in regions examined. The primary findings indicate that chronic MA exposure attenuates activation of select stress-associated brain regions, a dysregulation that might contribute to alterations in mood-related behaviors.