Corticotropin releasing factor: a key role in the neurobiology of addiction.
Drug addiction is a chronically relapsing disorder characterized by loss of control over intake and dysregulation of stress-related brain emotional systems. Since the discovery by Wylie Vale and his colleagues of corticotropin-releasing factor (CRF) and the structurally-related urocortins, CRF systems have emerged as mediators of the body's response to stress. Relatedly, CRF systems have a prominent role in driving addiction via actions in the central extended amygdala, producing anxiety-like behavior, reward deficits, excessive, compulsive-like drug self-administration and stress-induced reinstatement of drug seeking. CRF neuron activation in the medial prefrontal cortex may also contribute to the loss of control. Polymorphisms in CRF system molecules are associated with drug use phenotypes in humans, often in interaction with stress history. Drug discovery efforts have yielded brain-penetrant CRF1 antagonists with activity in preclinical models of addiction. The results support the hypothesis that brain CRF-CRF1 systems contribute to the etiology and maintenance of addiction.
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: ezorrilla@scripps.edu.
Eric P
EP
Zorrilla
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
Marian L
ML
Logrip
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
George F
GF
Koob
D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000209:etiology*
D003346:Corticotropin-Releasing Hormone
Acute or protracted withdrawal or abstinence; Alcohol or ethanol; Anxiety disorder; CRF or CRH or urocortin 1 or urocortin 2 or urocortin 3; Corticotropin-releasing factor or hormone receptor antagonist; Drug addiction or alcoholism or alcohol dependence or alcohol use disorder or binge drinking; Major depression; Stress-induced relapse or reinstatement or craving; Treatment or clinical trial