Effects of cannabinoids in Krox-24 targeted mice.
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.
Tzavara
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ET
INSERM U-99, Unité de Régulations des gènes et signalisation cellulaire, Hĵpital H. Mondor, Créteil, France.
Monory
K
K
Garel
S
S
Topilko
P
P
Charnay
P
P
Hanoune
J
J
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002186:Cannabinoids / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000235:genetics* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D017874:Immediate-Early Proteins; D008297:Male; D002189:Marijuana Abuse / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D002186:Cannabinoids; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014157:Transcription Factors; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases