Harper Kathryn M, Knapp Darin J, Park Meredith A, Breese George R
Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, School of Medicine, CB#7178, 3006 Thurston-Bowles Building, Chapel Hill, NC, 27599-7178, USA.
Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Psychopharmacology (Berl). 2017 Jan;234(1):79-88. doi: 10.1007/s00213-016-4439-y. Epub 2016 Sep 24.
Behavioral and neuroimmune vulnerability to withdrawal from chronic alcohol varies with age. The relation of anxiety-like behavior to amygdalar CCL2 responses following stress after withdrawal from chronic intermittent alcohol (CIA) was investigated in adolescent and adult rats.
Adolescent and adult Wistar rats were exposed to CIA (three 5-day blocks of dietary alcohol separated by 2 days of withdrawal) at concentrations that created similar blood alcohol levels across age. Twenty-four hours into the final withdrawal, half of the rats were exposed to 1 h of restraint stress. Four hours post-stress, rats were used for behavior or tissue assays.
Anxiety-like behavior was increased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 mRNA was increased versus controls by CIA in adolescents and by CIA and CIA + stress in adults. CCL2 co-localization with neuronal marker NeuN was decreased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 co-localization with astrocytic marker GFAP was decreased versus controls by CIA and CIA + stress in adolescents, but experimental groups did not differ from controls in adults. CCL2 co-localization with microglial marker Iba1 was decreased versus controls by stress alone in adolescents and by CIA + stress in adults.
Changes in CCL2 protein might control behavior at either age but are particularly associated with CIA alone in adolescents and with CIA + stress in adults. That the number of CeA neurons expressing CCL2 was altered after CIA and stress is consistent with CCL2 involvement in neural function.
慢性酒精戒断的行为和神经免疫易感性随年龄而异。研究了青春期和成年大鼠在慢性间歇性酒精（CIA）戒断后应激时，焦虑样行为与杏仁核CCL2反应之间的关系。
将青春期和成年Wistar大鼠暴露于CIA（三个5天的饮食酒精阶段，中间间隔2天戒断期），其浓度能使不同年龄段的大鼠血液酒精水平相似。在最后一次戒断的24小时，一半大鼠接受1小时的束缚应激。应激后4小时，大鼠用于行为或组织检测。
与对照组相比，青春期大鼠中CIA增加了焦虑样行为，成年大鼠中CIA + 应激增加了焦虑样行为。与对照组相比，青春期大鼠中CIA增加了CCL2 mRNA，成年大鼠中CIA、CIA + 应激均增加了CCL2 mRNA。与对照组相比，青春期大鼠中CIA降低了CCL2与神经元标志物NeuN的共定位，成年大鼠中CIA + 应激降低了CCL2与神经元标志物NeuN的共定位。与对照组相比，青春期大鼠中CIA和CIA + 应激均降低了CCL2与星形胶质细胞标志物GFAP的共定位，但成年大鼠的实验组与对照组无差异。与对照组相比，青春期大鼠中单独应激降低了CCL2与小胶质细胞标志物Iba1的共定位，成年大鼠中CIA + 应激降低了CCL2与小胶质细胞标志物Iba1的共定位。
CCL2蛋白的变化可能在两个年龄段都控制行为，但在青春期尤其与单独的CIA相关，在成年期与CIA + 应激相关。CIA和应激后表达CCL2的中央杏仁核神经元数量发生改变，这与CCL2参与神经功能一致。
