Frontiers in Pharmacology (Nov 2021)

Altered Cortico-Subcortical Network After Adolescent Alcohol Exposure Mediates Behavioral Deficits in Flexible Decision-Making

  • Alexander Gómez-A,
  • Carol A. Dannenhoffer,
  • Amanda Elton,
  • Amanda Elton,
  • Sung-Ho Lee,
  • Sung-Ho Lee,
  • Woomi Ban,
  • Yen-Yu Ian Shih,
  • Yen-Yu Ian Shih,
  • Yen-Yu Ian Shih,
  • Yen-Yu Ian Shih,
  • Charlotte A. Boettiger,
  • Charlotte A. Boettiger,
  • Charlotte A. Boettiger,
  • Charlotte A. Boettiger,
  • Donita L. Robinson,
  • Donita L. Robinson,
  • Donita L. Robinson

DOI
https://doi.org/10.3389/fphar.2021.778884
Journal volume & issue
Vol. 12

Abstract

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Behavioral flexibility, the ability to modify behavior according to changing conditions, is essential to optimize decision-making. Deficits in behavioral flexibility that persist into adulthood are one consequence of adolescent alcohol exposure, and another is decreased functional connectivity in brain structures involved in decision-making; however, a link between these two outcomes has not been established. We assessed effects of adolescent alcohol and sex on both Pavlovian and instrumental behaviors and resting-state functional connectivity MRI in adult animals to determine associations between behavioral flexibility and resting-state functional connectivity. Alcohol exposure impaired attentional set reversals and decreased functional connectivity among cortical and subcortical regions-of-interest that underlie flexible behavior. Moreover, mediation analyses indicated that adolescent alcohol-induced reductions in functional connectivity within a subnetwork of affected brain regions statistically mediated errors committed during reversal learning. These results provide a novel link between persistent reductions in brain functional connectivity and deficits in behavioral flexibility resulting from adolescent alcohol exposure.

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