Sex differences in responses of the basolateral-central amygdala circuit to alcohol, corticosterone and their interaction

Sex differences in responses of the basolateral-central amygdala circuit to alcohol, corticosterone and their interaction
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DOI:
10.1016/j.neuropharm.2016.11.021
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发表时间:
2017-03-01
期刊:
影响因子:
4.7
通讯作者:
Roberto, Marisa
Roberto, Marisa
中科院分区:
医学2区
文献类型:
--
作者:
Logrip, Marian L.;Oleata, Christopher;Roberto, Marisa

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酒精使用障碍是一种长期复发的疾病,对我们的社会构成了重大的健康挑战。压力是引发复发的普遍因素,尤其是对女性而言,然而酒精和压力相互作用的机制,以及这在男性和女性之间的差异,仍然知之甚少。连接杏仁核基底外侧核(BLA)和中央核(CeA)的谷氨酸能回路可能是这种适应的一个位点,但酒精、皮质酮及其相互作用对该回路的影响尚未得到充分研究。特别是,没有研究涉及这些影响的性别差异或中央核外侧和内侧细分之间潜在的差异反应。因此,我们评估了酒精和皮质酮治疗对雄性和雌性大鼠内侧和外侧CeA神经元中bla诱发的复合谷氨酸能反应的影响。在雄性大鼠中,我们观察到内侧和外侧CeA对酒精和皮质酮的反应差异很小,它们主要对酒精诱导的谷氨酸能突触后电位的抑制敏感。与雄性神经元不同,雌性大鼠的细胞对酒精抑制作用的敏感性降低。此外,雌性神经元对皮质酮的敏感性存在差异,皮质酮治疗后,外侧CeA神经元的反应明显减弱,内侧CeA神经元在皮质酮或随后的酒精联合应用下基本不变。总之,这些数据突出了男性和女性杏仁核对酒精和应激激素皮质酮的反应的显著差异,这些因素可能会影响性别对酒精和压力相关疾病的不同易感性。(C) 2016 Elsevier Ltd.版权所有。
Alcohol use disorders are chronically relapsing conditions that pose significant health challenges for our society. Stress is a prevalent trigger of relapse, particularly for women, yet the mechanisms by which alcohol and stress interact, and how this differs between males and females, remain poorly understood. The glutamatergic circuit connecting the basolateral (BLA) and central (CeA) nuclei of the amygdala is a likely locus for such adaptations, yet the impact of alcohol, corticosterone and their interaction on this circuit has been understudied. In particular, no studies have addressed sex differences in these effects or potential differential responses between the lateral and medial subdivisions of the central nucleus. Thus, we assessed the effects of alcohol and corticosterone treatments on BLA-evoked compound glutamatergic responses in medial and lateral CeA neurons from male and female rats. We observed minimal differences between medial and lateral CeA responses to alcohol and corticosterone in male rats, which were primarily sensitive to alcohol-induced inhibition of glutamatergic postsynaptic potentials. Unlike male neurons, cells from female rats displayed reduced sensitivity to alcohol's inhibitory effects. In addition, female neurons diverged in their sensitivity to corticosterone, with lateral CeA neuronal responses significantly blunted following corticosterone treatment and medial CeA neurons largely unchanged by corticosterone or subsequent co-application of alcohol. Together these data highlight striking differences in how male and female amygdala respond to alcohol and the stress hormone corticosterone, factors which may impact differential susceptibility of the sexes to alcohol- and stress-related disorders. (C) 2016 Elsevier Ltd. All rights reserved.