Role for Hippocampal δ-GABAA Receptors in the Effects of Adolescent Alcohol Exposure on Endocrine or Behavioral Stress Reactivity in Adulthood

Megan Tran
Megan Tran

Megan is a rising senior (‘22) majoring in Neuroscience & Behavior, and minoring in the College of East Asian Studies and Chemistry. She was born and raised in San Diego, CA, where she attended Torrey Pines High School. After graduating, she hopes to attend medical school. At Wesleyan, she also enjoys being a Peer Health Advocate, member of the Varsity Women’s Tennis team, and coordinator for the College of East Asian Studies Outreach program.

Abstract: Adolescent binge drinking is linked to abnormal stress reactivity in adulthood and increased vulnerability to developing anxiety disorders. However, the neuronal mechanisms driving this relationship are unknown. Though previous research focused on plasticity of the hypothalamic-pituitary-adrenal (HPA) axis, recent work has highlighted the importance of the hippocampus in regulating both stress and anxiety. Our prior work in adults showed that ethanol exposure in mice was associated with enhanced anxiety and increased GABAergic inhibition mediated by δ-subunit-containing GABAA receptors (δ-GABAARs) on parvalbumin (PV) interneurons in the hippocampus (Melón et al., 2019). The present study aims to determine whether the impact of adolescent alcohol exposure on stress reactivity in adulthood involves changes in δ-GABAA receptor expression in PV interneurons across the dorsal and ventral hippocampus. Adolescent male and female C57BL/6J had two weeks of daily limited access to alcohol (20% v/v) in a protocol that produces binge drinking. Following a two day withdrawal period, the mice completed a marble burying test and a three-chamber sociability test to assess anxiety-like behavior. Corticosterone (CORT), the main adrenal glucocorticoid in mice, was measured before and after a forced swim and acute social stressor. Brains were harvested and dorsal hippocampal tissue was probed and imaged for PV and δ-GABAAR protein expression. Analysis found no difference in δ-GABAAR nor PV expression based on adolescent drinking. A history of adolescent drinking was associated with a significant increase in basal CORT for females (p=0.03) but not males. Adolescent binge drinking did not impact basal anxiety-like behaviors in the marble burying nor sociability tests. Future work will examine this relationship across a greater sample size, and further consider the effects of sex and other potential residual effects of δ-GABAA expression. 

Video:

https://youtu.be/sFx67vjGFCE

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