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How Does Stress-Induced Activation of the Kappa Opioid System Increase Addiction Risk?

  • Charles Chavkin
    Correspondence
    Address correspondence to Charles Chavkin, Ph.D., Neuroscience Graduate Program and Department of Pharmacology, University of Washington School of Medicine, Room 425 HSB, Box 357280, Seattle, WA 98195-7280
    Affiliations
    Neuroscience Graduate Program and Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington
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  • Jonathan M. Ehrich
    Affiliations
    Neuroscience Graduate Program and Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington
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      In their article in this issue of Biological Psychiatry, Polter et al. (
      • Polter A.M.
      • Bishop R.A.
      • Briand L.A.
      • Graziane N.M.
      • Pierce R.C.
      • Kauer J.A.
      Poststress block of kappa opioid receptors rescues long-term potentiation of inhibitory synapses and prevents reinstatement of cocaine seeking.
      ) show that cold-water swim stress exposure blocks long-term potentiation of GABAergic synaptic input (LTPGABA) recorded in ventral tegmental area (VTA) dopamine neurons of male Sprague-Dawley rats. The effects of stress exposure on LTPGABA were blocked by pretreatment with the glucocorticoid antagonist RU-486 or the kappa opioid receptor (KOR) antagonist norbinaltorphimine (norBNI). When norBNI was given 4 days after stress exposure, it reversed the effects of swim stress on LTPGABA and blocked stress-induced reinstatement of cocaine self-administration. Because stress exposure is such a well-recognized risk factor for the development of compulsive drug abuse and relapse during intervals of abstinence, the findings that norBNI given after stress exposure could promote stress resilience and reverse the adverse effects of prior stress exposure are important preclinical advances in the development of addiction therapies. The study by Polter et al. also increases our understanding of the complex effects of stress on the reward circuitry controlling addictive drug effects.
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