Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal

• Published in: Science (American Association for the Advancement of Science) 1997-06, Vol.276 (5321), p.2050-2054
• Main Authors: de Fonseca, Fernando Rodríguez, M. Rocío A. Carrera, Navarro, Miguel, Koob, George F., Weiss, Friedbert
• Format: Article
• Language: English
• Subjects: Amygdala; Amygdala - drug effects; Amygdala - metabolism; Animals; Anxiety; Anxiety - chemically induced; Behavior, Animal - drug effects; Behavioral neuroscience; Behavioral psychophysiology; Biological and medical sciences; Brain; Brain - drug effects; Brain - metabolism; Cannabinoids; Cannabis; Cocaine; Corticosterone; Corticosterone - blood; Corticotropin releasing hormone; Corticotropin-Releasing Hormone - metabolism; Dosage; Dronabinol - adverse effects; Dronabinol - analogs & derivatives; Dronabinol - antagonists & inhibitors; Dronabinol - pharmacology; Drug addiction; Drug dependence; Drug Rehabilitation; Emotional Response; Experimental Groups; Fear of Success; Feedback (Response); Fundamental and applied biological sciences. Psychology; Hormones and behavior; Limbic system; Logical Thinking; Male; Marijuana; Medical research; Microdialysis; Narcotics; Neurology; Piperidines - pharmacology; Proto-Oncogene Proteins c-fos - analysis; Psychological Patterns; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Pyrazoles - pharmacology; Rats; Rats, Wistar; Receptors, Cannabinoid; Receptors, Drug - antagonists & inhibitors; Rimonabant; Studies; Substance Abuse; Substance Withdrawal Syndrome - metabolism; Vehicles
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.276.5321.2050

Corticotropin-releasing factor (CRF) has been implicated in the mediation of the stress-like and negative affective consequences of withdrawal from drugs of abuse, such as alcohol, cocaine, and opiates. This study sought to determine whether brain CRF systems also have a role in cannabinoid dependence. Rats were treated daily for 2 weeks with the potent synthetic cannabinoid HU-210. Withdrawal, induced by the cannabinoid antagonist SR 141716A, was accompanied by a marked elevation in extracellular CRF concentration and a distinct pattern of Fos activation in the central nucleus of the amygdala. Maximal increases in CRF corresponded to the time when behavioral signs resulting from cannabinoid withdrawal were at a maximum. These data suggest that long-term cannabinoid administration alters CRF function in the limbic system of the brain, in a manner similar to that observed with other drugs of abuse, and also induces neuroadaptive processes that may result in future vulnerability to drug dependence.