Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits

Nat Commun. 2018 Jan 15;9(1):211. doi: 10.1038/s41467-017-02615-9.


Addiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basal Ganglia / drug effects*
  • Basal Ganglia / metabolism
  • Basal Ganglia / physiology
  • Brain / cytology
  • Brain / drug effects
  • Brain / physiology
  • Central Nervous System Depressants / pharmacology
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Ethanol / pharmacology*
  • Habits*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net / drug effects*
  • Nerve Net / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology


  • Central Nervous System Depressants
  • Ethanol