University of Wisconsin–Madison

Stress Neuroadaptations in Addiction

Preclinical animal models have convincingly demonstrated that stress neuroadaptations in response to chronic alcohol and other drug (AOD) use play an important role in addiction etiology and relapse following treatment. My laboratory has been instrumental in translating these findings from animals to human AOD users. We have also demonstrated that these stress neuroadaptations manifest as exaggerated reactivity selectively to unpredictable or otherwise uncertain stressors. These studies implicate the corticotropin-releasing factor (CRF) and noradrenergic (NE) neurotransmitter systems as potential partial mediators of these stress neuroadaptations and we have initiated research to confirm this via pharmacological manipulation of these neurotransmitter systems. Pharmacological or behavioral manipulation of the CRF and NE stress systems also emerges as innovative interventions suggested by this body of research.


  • Kaye JT, Bradford DE, Magruder KP & Curtin JJ (in press). Probing for neuroadaptations to unpredictable stresors in addiction: translational methods and emerging evidence. Journal of Studies on Alcohol and Drugs, 78, 353-371.PDF | OSF
  • Moberg CA, Bradford DE, Kaye JT, Curtin JJ (2017). Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans. Journal of Abnormal Psychology, 126(4), 441-453. PMC5418084. PDF | OSF
  • Bradford DE, Shapiro BL, Curtin JJ (2013). How bad could it be? Alcohol dampens stress responses to uncertain intensity threat. Psychological Science, 24, 2541-2549. PMC3951286. PDF | Study highlights
  • Hefner KR, Moberg CA, Hachiya, LY, Curtin JJ (2013). Alcohol stress response dampening during imminent vs. distal, uncertain threat. Journal of Abnormal Psychology, 122, 756-769. PMC4047525. PDF
  • Hogle JM, Kaye JT, Curtin JJ (2010). Nicotine withdrawal increases threat-induced anxiety but not fear: Neuroadaptation in human addiction. Biological Psychiatry, 68, 719-725. PMC2949532. PDF | Study highlights
  • Moberg CA, Curtin JJ (2009). Alcohol selectively reduces anxiety but not fear: Startle response during unpredictable vs. predictable threat. Journal of Abnormal Psychology, 118, 335-347. PMC2756160. PDF