The endogenous cannabinoid system controls extinction of aversive memories.

Giovanni Marsicano, Carsten T. Wotjak, Shahnaz C. Azad, Tiziana Bisogno, Gerhard Rammes, Maria Grazia Cascio, Heike Hermann, Jianrong Tang, Clementine Hofmann, Walter Zieglgänsberger, Vincenzo Di Marzo, Beat Lutz
Nature. 2002-08-01; 418(6897): 530-534
DOI: 10.1038/nature00839

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1. Nature. 2002 Aug 1;418(6897):530-4.

The endogenous cannabinoid system controls extinction of aversive memories.

Marsicano G(1), Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H,
Tang J, Hofmann C, Zieglgänsberger W, Di Marzo V, Lutz B.

Author information:
(1)Molecular Genetics of Behaviour, Max Planck Institute of Psychiatry,
Kraepelinstrasse 2-10, 80804 Munich, Germany.

Comment in
Nature. 2002 Aug 1;418(6897):488-9.

Acquisition and storage of aversive memories is one of the basic principles of
central nervous systems throughout the animal kingdom. In the absence of
reinforcement, the resulting behavioural response will gradually diminish to be
finally extinct. Despite the importance of extinction, its cellular mechanisms
are largely unknown. The cannabinoid receptor 1 (CB1) and endocannabinoids are
present in memory-related brain areas and modulate memory. Here we show that the
endogenous cannabinoid system has a central function in extinction of aversive
memories. CB1-deficient mice showed strongly impaired short-term and long-term
extinction in auditory fear-conditioning tests, with unaffected memory
acquisition and consolidation. Treatment of wild-type mice with the CB1
antagonist SR141716A mimicked the phenotype of CB1-deficient mice, revealing that
CB1 is required at the moment of memory extinction. Consistently, tone
presentation during extinction trials resulted in elevated levels of
endocannabinoids in the basolateral amygdala complex, a region known to control
extinction of aversive memories. In the basolateral amygdala, endocannabinoids
and CB1 were crucially involved in long-term depression of GABA
(gamma-aminobutyric acid)-mediated inhibitory currents. We propose that
endocannabinoids facilitate extinction of aversive memories through their
selective inhibitory effects on local inhibitory networks in the amygdala.

DOI: 10.1038/nature00839
PMID: 12152079 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus