Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal.
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.
Rodríguez de Fonseca
F
F
Instituto Complutense de Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, 28223 Madrid, Spain.
Carrera
M R
MR
Navarro
M
M
Koob
G F
GF
Weiss
F
F
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D013759:Dronabinol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D010880:Piperidines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; D003346:Corticotropin-Releasing Hormone; C062018:HU 211; D000077285:Rimonabant; D003345:Corticosterone