Neuron
Volume 98, Issue 3, 2 May 2018, Pages 512-520.e6
Journal home page for Neuron

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

https://doi.org/10.1016/j.neuron.2018.03.033Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Contexts exert bi-directional control over extinction and reinstatement of reward seeking

  • AcbSh Drd1 projections to the VTA control reinstatement

  • AcbSh Drd1 projections to the LH control extinction

  • Gad1 neurons in the VTA and LH control reinstatement and extinction, respectively

Summary

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
relapse
abstinence
hypothalamus
ventral tegmental area
ventral striatum

Cited by (0)

5

Lead Contact