Alcohol dependence and withdrawal impair serotonergic regulation of GABA transmission in the rat central nucleus of the amygdala

Sophia Khom, Sarah A. Wolfe, Reesha R. Patel, Dean Kirson, David M. Hedges, Florence P. Varodayan, Michal Bajo, Marisa Roberto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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 Accordingly, 5-HT abolished spontaneous neuronal firing in naive and dependent rats but had bidirectional effects in withdrawn.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.

Original languageEnglish (US)
Pages (from-to)6842-6853
Number of pages12
JournalJournal of Neuroscience
Issue number36
StatePublished - Sep 2 2020


  • Alcohol use disorder
  • Central amygdala
  • Electrophysiology
  • Ethanol
  • GABA
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)


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