Chronic intermittent ethanol exposure disrupts stress-related tripartite communication to impact affect-related behavioral selection in male rats.
Chronic intermittent ethanol exposure disrupts stress-related tripartite communication to impact affect-related behavioral selection in male rats.
复制标题
DOI：
10.1016/j.ynstr.2023.100539
复制
发表时间：
2023-05
影响因子：
5
通讯作者：
O'Neill, P. R.
中科院分区：
文献类型：
--
作者：
Munier, J. J.;Rahal, D.;Shen, S.;Hanna, A.;Marty, V. N.;Fanselow, M. S.;Spigelman, I.;O'Neill, P. R.
酒精使用障碍（AUD）的特征是摄入控制丧失，焦虑增加，易受复发诱导的压力。在动物模型中，星形胶质细胞和神经元都有助于慢性间歇性乙醇（CIE）暴露的行为和激素后果。关于CIE如何破坏下丘脑神经胶质细胞通讯的细节，这介导了压力反应，目前还缺乏。我们进行了一个行为电池（梳理，开放领域，反应一个单一的，无线索的脚电击，不情愿的访问两瓶选择乙醇饮用），然后在离体切片的下丘脑室旁核（PVN）从雄性大鼠暴露于CIE蒸汽或空气暴露的控制Ca 2+成像。在有或没有选择性α-肾上腺素能受体（αAR）或含GluN 2B的N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂的情况下，评价了对去甲肾上腺素（NE）的反应，然后用地塞米松（DEX）模拟药理学应激反应。不出所料，CIE大鼠改变了焦虑样，饲养，梳理和饮酒行为。重要的是，NE介导的Ca 2+事件频率的降低在CIE神经元和星形胶质细胞中均被钝化。给予选择性α 1 AR拮抗剂哌唑嗪可逆转这两种细胞类型中CIE诱导的功能障碍。此外，药理学应激方案逆转了CIE星形胶质细胞的改变的基础Ca 2+信号传导谱。星形胶质细胞对NE反应的信号变化与焦虑样行为相关，如梳理：饲养比例，这表明三方突触功能在探索和压力应对行为之间的转换中起着重要作用。这些数据显示了CIE暴露如何导致PVN神经胶质功能的持续变化，并为这些生理变化如何在行为选择中表现提供了基础。CIE产生的变化，情感和完善的行为具有相当大的组内变异。CIE减弱PVN神经元和星形胶质细胞对神经内分泌药理学应激的Ca 2+反应。CIE诱导的α1-肾上腺素受体功能上调损害了应激反应中的三方通讯CIE诱导的PVN神经胶质功能变化与行为电池反应改变相关。
Alcohol use disorder (AUD) is characterized by loss of intake control, increased anxiety, and susceptibility to relapse inducing stressors. Both astrocytes and neurons contribute to behavioral and hormonal consequences of chronic intermittent ethanol (CIE) exposure in animal models. Details on how CIE disrupts hypothalamic neuro-glial communication, which mediates stress responses are lacking. We conducted a behavioral battery (grooming, open field, reactivity to a single, uncued foot-shock, intermittent-access two-bottle choice ethanol drinking) followed by Ca2+ imaging in ex-vivo slices of paraventricular nucleus of the hypothalamus (PVN) from male rats exposed to CIE vapor or air-exposed controls. Ca2+ signals were evaluated in response to norepinephrine (NE) with or without selective α-adrenergic receptor (αAR) or GluN2B-containing N-methyl-D-aspartate receptor (NMDAR) antagonists, followed by dexamethasone (DEX) to mock a pharmacological stress response. Expectedly, CIE rats had altered anxiety-like, rearing, grooming, and drinking behaviors. Importantly, NE-mediated reductions in Ca2+ event frequency were blunted in both CIE neurons and astrocytes. Administration of the selective α1AR antagonist, prazosin, reversed this CIE-induced dysfunction in both cell types. Additionally, the pharmacological stress protocol reversed the altered basal Ca2+ signaling profile of CIE astrocytes. Signaling changes in astrocytes in response to NE were correlated with anxiety-like behaviors, such as the grooming:rearing ratio, suggesting tripartite synaptic function plays a role in switching between exploratory and stress-coping behavior. These data show how CIE exposure causes persistent changes to PVN neuro-glial function and provides the groundwork for how these physiological changes manifest in behavioral selection. CIE produces changes to affective and consummatory behaviors with considerable intra-group variability. CIE blunts Ca2+ responses of PVN neurons and astrocytes to neuroendocrine pharmacological stress. CIE-induced upregulation of α1-adrenoceptor function impairs tripartite communication in response to stress. CIE-induced changes to PVN neuro-glial function correlate to altered behavioral battery responses.
登录
查看更多内容
影响因子：
25
作者：
Chen J;Poskanzer KE;Freeman MR;Monk KR
通讯作者：
Monk KR
影响因子：
14.8
作者：
Kalueff, Allan V.;Aldridge, J. Wayne;Tuohimaa, Pentti
通讯作者：
Tuohimaa, Pentti
影响因子：
3.6
作者：
Getachew, Bruk;Hauser, Sheketha R.;Tizabi, Yousef
通讯作者：
Tizabi, Yousef
慢性间歇性乙醇暴露后，α-肾上腺素受体功能的性别差异导致下丘脑化生性受损。
DOI：
10.1111/acer.14900
发表时间：
2022-08
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
--
作者：
Munier, Joseph J.;Marty, Vincent N.;Spigelman, Igor
通讯作者：
Spigelman, Igor
影响因子：
20.8
作者：
Jin S;Cao Q;Yang F;Zhu H;Xu S;Chen Q;Wang Z;Lin Y;Cinar R;Pawlosky RJ;Zhang Y;Xiong W;Gao B;Koob GF;Lovinger DM;Zhang L
通讯作者：
Zhang L