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Psychology
Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal
Fernando Rodríguez de Fonseca, * M. Rocío A. Carrera, Miguel Navarro, * George F. Koob, Friedbert Weiss
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.
F. Rodríguez de Fonseca and M. Navarro, Instituto Complutense de Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, 28223 Madrid, Spain. M. R. A. Carrera, G. F. Koob, F. Weiss, Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
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