The neurobiology of addiction develops over a course of repeated drug abuse and/or stress. Changes in neurobiology underline altered mood and cognition related to increased limbic negative affect and loss of frontal cortical behavioral control. Drug abuse, stress and other factors increase NF-κB transcription of multiple proinflammatory genes that spread across brain cell types further amplifying of NF-κB transcription through loops involving cytokines, chemokines, oxidases and proteases. Evidence supports the spread and persistence of brain innate immune gene induction as creating the neurobiology of addiction. Human studies of genetic risk for alcoholism and post-mortem brain support the role of innate immune genes in addiction. Animal behavior studies indicate increasing drug consumption and mounting negative affect and depression-like behavior are due to innate immune gene induction. Further, frontal cortical hyperexcitability, behavioral flexibility and loss of behavioral control can all be linked to innate immune genes. Together these finding suggest the neurobiology of addiction is due to innate immune gene altered signaling inducing the behaviors that define addiction. Therapies that blunt brain innate immune gene induction may represent new and novel approaches to preventing and/or reversing addiction.
