The Role of NFkB in Drug Addiction: Beyond Inflammation

Alcohol Alcohol. 2017 Mar 9;52(2):172-179. doi: 10.1093/alcalc/agw098.


Aims: Nuclear factor kappa light chain enhancer of activated B cells (NFkB) is a ubiquitous transcription factor well known for its role in the innate immune response. As such, NFkB is a transcriptional activator of inflammatory mediators such as cytokines. It has recently been demonstrated that alcohol and other drugs of abuse can induce NFkB activity and cytokine expression in the brain. A number of reviews have been published highlighting this effect of alcohol, and have linked increased NFkB function to neuroimmune-stimulated toxicity. However, in this review we focus on the potentially non-immune functions of NFkB as possible links between NFkB and addiction.

Methods: An extensive review of the literature via Pubmed searches was used to assess the current state of the field.

Results: NFkB can induce the expression of a diverse set of gene targets besides inflammatory mediators, some of which are involved in addictive processes, such as opioid receptors and neuropeptides. NFkB mediates complex behaviors including learning and memory, stress responses, anhedonia and drug reward, processes that may lie outside the role of NFkB in the classic neuroimmune response.

Conclusions: Future studies should focus on these non-immune functions of NFkB signaling and their association with addiction-related processes.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anhedonia / physiology
  • Behavior, Addictive / genetics
  • Behavior, Addictive / physiopathology
  • Gene Expression Regulation*
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Learning / physiology
  • Memory / physiology
  • NF-kappa B / immunology
  • NF-kappa B / physiology*
  • Neuropeptides / biosynthesis
  • Receptors, Opioid / biosynthesis
  • Substance-Related Disorders / genetics*
  • Substance-Related Disorders / physiopathology*


  • NF-kappa B
  • Neuropeptides
  • Receptors, Opioid