Adolescent alcohol exposure decreases frontostriatal resting-state functional connectivity in adulthood

Addict Biol. 2018 Mar;23(2):810-823. doi: 10.1111/adb.12530. Epub 2017 Jul 9.

Abstract

Connectivity of the prefrontal cortex (PFC) matures through adolescence, coinciding with emergence of adult executive function and top-down inhibitory control over behavior. Alcohol exposure during this critical period of brain maturation may affect development of PFC and frontolimbic connectivity. Adult rats exposed to adolescent intermittent ethanol (AIE; 5 g/kg ethanol, 25 percent v/v in water, intragastrically, 2-day-on, 2-day-off, postnatal day 25-54) or water control underwent resting-state functional MRI to test the hypothesis that AIE induces persistent changes in frontolimbic functional connectivity under baseline and acute alcohol conditions (2 g/kg ethanol or saline, intraperitoneally administered during scanning). Data were acquired on a Bruker 9.4-T MR scanner with rats under dexmedetomidine sedation in combination with isoflurane. Frontolimbic network regions-of-interest for data analysis included PFC [prelimbic (PrL), infralimbic (IL), and orbitofrontal cortex (OFC) portions], nucleus accumbens (NAc), caudate putamen (CPu), dorsal hippocampus, ventral tegmental area, amygdala, and somatosensory forelimb used as a control region. AIE decreased baseline resting-state connectivity between PFC subregions (PrL-IL and IL-OFC) and between PFC-striatal regions (PrL-NAc, IL-CPu, IL-NAc, OFC-CPu, and OFC-NAc). Acute ethanol induced negative blood-oxygen-level-dependent changes within all regions of interest examined, along with significant increases in functional connectivity in control, but not AIE animals. Together, these data support the hypothesis that binge-like adolescent alcohol exposure causes persistent decreases in baseline frontolimbic (particularly frontostriatal) connectivity and alters sensitivity to acute ethanol-induced increases in functional connectivity in adulthood.

Keywords: Sprague-Dawley; adolescence; ethanol; fcMRI; prefrontal cortex; striatum.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / diagnostic imaging
  • Amygdala / drug effects
  • Animals
  • Binge Drinking
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / drug effects
  • Central Nervous System Depressants / pharmacology*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects*
  • Disease Models, Animal
  • Ethanol / pharmacology*
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / drug effects*
  • Functional Neuroimaging
  • Hippocampus / diagnostic imaging
  • Hippocampus / drug effects
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / drug effects
  • Nucleus Accumbens / diagnostic imaging
  • Nucleus Accumbens / drug effects
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / drug effects
  • Putamen / diagnostic imaging
  • Putamen / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Rest
  • Underage Drinking
  • Ventral Tegmental Area / diagnostic imaging
  • Ventral Tegmental Area / drug effects

Substances

  • Central Nervous System Depressants
  • Ethanol