Targeting the intracellular signaling "STOP" and "GO" pathways for the treatment of alcohol use disorders

Psychopharmacology (Berl). 2018 Jun;235(6):1727-1743. doi: 10.1007/s00213-018-4882-z. Epub 2018 Apr 14.


In recent years, research has identified the molecular and neural substrates underlying the transition of moderate "social" consumption of alcohol to the characteristic alcohol use disorder (AUD) phenotypes including excessive and compulsive alcohol use which we define in the review as the GO signaling pathways. In addition, growing evidence points to the existence of molecular mechanisms that keep alcohol consumption in check and that confer resilience for the development of AUD which we define herein as the STOP signaling pathways. In this review, we focus on examples of the GO and the STOP intracellular signaling pathways and discuss our current knowledge of how manipulations of these pathways may be used for the treatment of AUD.

Keywords: Addiction; Alcohol; BDNF; Fyn; GDNF; Medication Development; Signaling; Translation; mTOR.

Publication types

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

MeSH terms

  • Alcohol Drinking / drug therapy
  • Alcohol Drinking / metabolism
  • Alcoholism / drug therapy*
  • Alcoholism / metabolism*
  • Animals
  • Benzodioxoles / administration & dosage
  • Benzodioxoles / metabolism
  • Brain-Derived Neurotrophic Factor / antagonists & inhibitors
  • Brain-Derived Neurotrophic Factor / metabolism
  • Drug Delivery Systems / methods*
  • Ethanol / administration & dosage
  • Humans
  • Intracellular Fluid / drug effects
  • Intracellular Fluid / metabolism*
  • Quinazolines / administration & dosage
  • Quinazolines / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sirolimus / administration & dosage
  • Sirolimus / metabolism
  • Treatment Outcome


  • Benzodioxoles
  • Brain-Derived Neurotrophic Factor
  • Quinazolines
  • Ethanol
  • saracatinib
  • Sirolimus