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Role of Corticotropin-Releasing Factor in Drug Addiction

Potential for Pharmacological Intervention


Drug dependence is a chronically relapsing disorder that places an enormous strain on healthcare systems. For treatments to have long-term clinical value, they must address the causes of relapse. Corticotropin-releasing factor (CRF), a neuropeptide central to the stress response, may be one key to solving the relapse cycle. CRF is hypothesized to mediate the elevated anxiety and negative emotional states experienced during the development of dependence. This review summarizes existing data on changes in the CRF system produced by drugs of abuse and the function of CRF receptors in regulating behavioural responses to drugs of abuse, with an emphasis on drug dependence. Drug-induced changes in neuronal excitability throughout the limbic system, as well as the reversal of these neuroadaptations by CRF receptor antagonists, are also addressed. CRF receptor antagonists, by reducing the motivational effects of drug withdrawal and protracted abstinence, are proposed to be novel therapeutic targets for drug abuse and addiction.

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The authors would like to thank Michael Arends for editorial assistance in the preparation of this manuscript and Janet Hightower for help with figure preparation. Financial support was received from the Pearson Center for Alcoholism and Addiction Research and National Institutes of Health grant DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases, AA06420, AA08459 and AA018914 from the National Institute on Alcohol Abuse and Alcoholism, and DA04043, DA04398 and DA023957 from the National Institute on Drug Abuse. G.F. Koob and E.P. Zorrilla are inventors on a provisional patent filed for CRF1 antagonists (US provisional patent number 60/902,479). M.L. Logrip has no conflicts of interest to disclose. This is publication number 20696 from The Scripps Research Institute.

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Logrip, M.L., Koob, G.F. & Zorrilla, E.P. Role of Corticotropin-Releasing Factor in Drug Addiction. CNS Drugs 25, 271–287 (2011). https://doi.org/10.2165/11587790-000000000-00000

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  • CRF1 Receptor
  • Extended Amygdala
  • CRF1 Receptor Antagonist
  • Ventral Tegmental Area Neuronal Activity