Zuloaga Damian G, Johnson Lance A, Weber Sydney, Raber Jacob
Department of Behavioral Neuroscience, Oregon Health and Science University Portland, Portland, OR, 97239, USA.
Department of Psychology, University at Albany, Albany, NY, 12222, USA.
Psychopharmacology (Berl). 2016 Feb;233(3):381-92. doi: 10.1007/s00213-015-4114-8. Epub 2015 Nov 2.
Chronic methamphetamine (MA) abuse leads to dependence and symptoms of withdrawal after use has ceased. Negative mood states associated with withdrawal, as well as drug reinstatement, have been linked to drug-induced disruption of the hypothalamic-pituitary-adrenal (HPA) axis. However, effects of chronic MA exposure or acute MA exposure following withdrawal on neural activation patterns within brain regions that regulate the HPA axis are unknown.
In this study, neural activation patterns were assessed by quantification of c-Fos protein in mice exposed to different regimens of MA administration.
(Experiment 1) Adult male mice were treated with MA (5 mg/kg) or saline once or once daily for 10 days. (Experiment 2) Mice were treated with MA or saline once daily for 10 days and following a 10-day withdrawal period were re-administered a final dose of MA or saline. c-Fos was quantified in brains after the final injection.
(Experiment 1) Compared to exposure to a single dose of MA (5 mg/kg), chronic MA exposure decreased the number of c-Fos expressing cells in the paraventricular hypothalamus, dorsomedial hypothalamus, central amygdala, basolateral amygdala, bed nucleus of the stria terminalis (BNST), and CA3 hippocampal region. (Experiment 2) Compared to mice receiving their first dose of MA, mice chronically treated with MA, withdrawn, and re-administered MA, showed decreased c-Fos expressing cells within the central and basolateral amygdala, BNST, and CA3.
HPA axis-associated amygdala, extended amygdala, and hippocampal regions endure lasting effects following chronic MA exposure and therefore may be linked to stress-related withdrawal symptoms.
长期滥用甲基苯丙胺（MA）会导致成瘾，并在停止使用后出现戒断症状。与戒断相关的负面情绪状态以及药物复吸，都与药物引起的下丘脑-垂体-肾上腺（HPA）轴功能紊乱有关。然而，长期暴露于MA或戒断后急性暴露于MA对调节HPA轴的脑区内神经激活模式的影响尚不清楚。
在本研究中，通过对接受不同MA给药方案的小鼠体内c-Fos蛋白进行定量，评估神经激活模式。
（实验1）成年雄性小鼠接受MA（5mg/kg）或生理盐水注射，单次注射或每日注射一次，共10天。（实验2）小鼠每日接受MA或生理盐水注射，共10天，在10天的戒断期后，再次给予最后一剂MA或生理盐水。最后一次注射后，对大脑中的c-Fos进行定量。
（实验1）与单次注射MA（5mg/kg）相比，长期暴露于MA会减少室旁下丘脑、背内侧下丘脑、中央杏仁核、基底外侧杏仁核、终纹床核（BNST）和海马CA3区中表达c-Fos的细胞数量。（实验2）与首次接受MA注射的小鼠相比，长期接受MA治疗、戒断后再次接受MA注射的小鼠，其中央杏仁核、基底外侧杏仁核、BNST和CA3区内表达c-Fos的细胞数量减少。
长期暴露于MA后，与HPA轴相关的杏仁核、扩展杏仁核和海马区会产生持久影响，因此可能与应激相关的戒断症状有关。
