Effects of cannabinoids in Krox-24 targeted mice.

Tzavara ET, Monory K, Garel S, Topilko P, Charnay P, Hanoune J.

INSERM U-99, Unite de Regulations des genes et signalisation cellulaire, Hjpital H. Mondor, Creteil, France.

Krox-24 is an immediate early gene encoding a zinc-finger transcription factor implicated in several adaptive responses, and its induction by cannabinoids has been reported. We used mice targeted in the Krox-24 gene to specifically dissect the role of this protein in the acute and chronic central actions of cannabinoids. We report here on the ability of cannabinoids to activate G-proteins and to inhibit adenylyl cyclase, and to elicit behavioral responses in wild-type and mutant mice. The behavioral parameters and the biochemical correlates of abstinence after delta9-THC withdrawal were evaluated. We show that Krox-24 is not involved in the acute analgesic effects of delta9-THC and in the SR precipitated delta9-THC withdrawal syndrome.