ACTIVATION OF CORTICOTROPIN-RELEASING FACTOR IN THE LIMBIC SYSTEM DURING CANNABINOID WITHDRAWAL

Corticotropin-releasing factor (CRF) has been implicated in the mediat ion of the stress-like and negative affective consequences oi withdraw al from drugs of abuse, such as alcohol, cocaine, and opiates. This st udy sought to determine whether brain CRF systems also have a role in cannabinoid dependence. Rats were treated daily for 2 weeks with the p otent synthetic cannabinoid HU-210. Withdrawal, induced by the cannabi noid antagonist SR 141716A, was accompanied by a marked elevation in e xtracellular CRF concentration and a distinct pattern of Fos activatio n in the central nucleus:of the amygdala. Maximal increases in CRF cor responded lo the time when behavioral signs resulting from cannabinoid withdrawal were at a maximum. These data suggest that long-term canna binoid 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 vu lnerability to drug dependence.