Distinct Accumbens Shell Output Pathways Promote versus Prevent Relapse to Alcohol Seeking

Neuron. 2018 May 2;98(3):512-520.e6. doi: 10.1016/j.neuron.2018.03.033. Epub 2018 Apr 12.


Contexts exert bi-directional control over relapse to drug seeking. Contexts associated with drug self-administration promote relapse, whereas contexts associated with the absence of self-administration protect against relapse. The nucleus accumbens shell (AcbSh) is a key brain region determining these roles of context. However, the specific cell types, and projections, by which AcbSh serves these dual roles are unknown. Here, we show that contextual control over relapse and abstinence is embedded within distinct output circuits of dopamine 1 receptor (Drd1) expressing AcbSh neurons. We report anatomical and functional segregation of Drd1 AcbSh output pathways during context-induced reinstatement and extinction of alcohol seeking. The AcbSh→ventral tegmental area (VTA) pathway promotes relapse via projections to VTA Gad1 neurons. The AcbSh→lateral hypothalamus (LH) pathway promotes extinction via projections to LH Gad1 neurons. Targeting these opposing AcbSh circuit contributions may reduce propensity to relapse to, and promote abstinence from, drug use.

Keywords: Renewal; abstinence; hypothalamus; relapse; ventral striatum; ventral tegmental area.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / metabolism*
  • Alcohol Drinking / prevention & control
  • Alcohol Drinking / psychology
  • Animals
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Drug-Seeking Behavior / drug effects
  • Drug-Seeking Behavior / physiology*
  • Ethanol / administration & dosage
  • Male
  • Neural Pathways / chemistry
  • Neural Pathways / physiology
  • Nucleus Accumbens / chemistry
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Recurrence
  • Self Administration


  • Ethanol