Alcohol Dependence and Withdrawal Impair Serotonergic Regulation of GABA Transmission in the Rat Central Nucleus of the Amygdala
Alcohol Dependence and Withdrawal Impair Serotonergic Regulation of GABA Transmission in the Rat Central Nucleus of the Amygdala
复制标题
酒精依赖和戒断损害大鼠杏仁核中央核中GABA传递的血清素能调节
DOI：
10.1523/jneurosci.0733-20.2020
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发表时间：
2020-09-02
影响因子：
5.3
通讯作者：
Roberto, Marisa
中科院分区：
文献类型：
--
作者：
Khom, Sophia;Wolfe, Sarah A.;Roberto, Marisa
Excessive serotonin (5-HT) signaling plays a critical role in the etiology of alcohol use disorder. The central nucleus of the amygdala (CeA) is a key player in alcohol-dependence associated behaviors. The CeA receives dense innervation from the dorsal raphe nucleus, the major source of 5-HT, and expresses 5-HT receptor subtypes (e.g., 5-HT2C and 5-HT1A) critically linked to alcohol use disorder. Notably, the role of 5-HT regulating rat CeA activity in alcohol dependence is poorly investigated. Here, we examined neuroadaptations of CeA 5-HT signaling in adult, male Sprague Dawley rats using an established model of alcohol dependence (chronic intermittent alcohol vapor exposure), ex vivo slice electrophysiology and ISH. 5-HT increased frequency of sIPSCs without affecting postsynaptic measures, suggesting increased CeA GABA release in naive rats. In dependent rats, this 5-HT-induced increase of GABA release was attenuated, suggesting blunted CeA 5-HT sensitivity, which partially recovered in protracted withdrawal (2 weeks). 5-HT increased vesicular GABA release in naive and dependent rats but had split effects (increase and decrease) after protracted withdrawal indicative of neuroadaptations of presynaptic 5-HT receptors. Accordingly, 5-HT abolished spontaneous neuronal firing in naive and dependent rats but had bidirectional effects in withdrawn. Alcohol dependence and protracted withdrawal did not alter either 5-HT1A-mediated decrease of CeA GABA release or Htr1a expression but disrupted 5-HT2C-signaling without affecting Htr2c expression. Collectively, our study provides detailed insights into modulation of CeA activity by the 5-HT system and unravels the vulnerability of the CeA 5-HT system to chronic alcohol and protracted withdrawal.
