Stress, dysregulation of drug reward pathways, and the transition to drug dependence.
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.
Committee on the Neurobiology of Addictive Disorders, the Scripps Research Institute, La Jolla, CA 92037, USA. gkoob@scripps.edu
George
G
Koob
Mary Jeanne
MJ
Kreek
D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D006854:Hydrocortisone / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology; D013287:Illicit Drugs / Q000009:adverse effects / Q000494:pharmacology; D008959:Models, Neurological; D011388:Prolactin / Q000502:physiology; D051381:Rats; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D013312:Stress, Physiological / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000209:etiology / Q000503:physiopathology*
D013287:Illicit Drugs; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone