Stress, Dysregulation of Drug Reward Pathways, and the Transition to Drug Dependence
Year: 2007
Type: article
Abstract: This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from limited access to drugs to long-term compulsive use of drugs. A dramatic escalation in drug intake with extended access to drug self-administration is characterized by a dysregulation of brain reward pathways. Hormonal studies using an experimenter-administered cocaine binge model and an escalation self-administration model have revealed large increases in ACTH and corticosterone in rats during an acute binge with attenuation during the chronic binge stage and a reactivation of the hypothalamic-pituitary-adrenal axis during acute withdrawal. The activation of the hypothalamic-pituitary-adrenal axis with cocaine appears to depend on feed-forward activation of the mesolimbic dopamine system. At the same time, escalation in drug intake with either extended access or dependence-induction produces an activation of the brain stress system's corticotropin-releasing factor outside of the hypothalamus in the extended amygdala, which is particularly evident during acute withdrawal. A model of the role of different levels of hormonal/brain stress activation in addiction is presented that has heuristic value for understanding individual vulnerability to drug dependence and novel treatments for the disorder.
Source: American Journal of Psychiatry
Authors: George Koob,, Mary Jeanne Kreek
Institution: Scripps Research Institute
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Neuropharmacology of Ethanol Reinforcement, G1550850040, G1795660798, G2137500120, G2229086814, G2475497404, G2534244385, TREATMENT OF ADDICTIONS--BIOLOGICAL CORRELATES, G3720365366, Addictive Drugs-Pharmacology & Physiology, Transforming Translational Science and Education to Benefit Human Health, G429745982, G431812084, G4332683981, G56130422, G590716232, G5973581827, G5974863992, Substance Abuse and HIV: Genetics and Disease Progression, G7636921007, G8471695710, G8725389344, CNS Effects of Alcohol: Cellular Neurobiology
OpenAlex ID: W2166133075