The endogenous cannabinoid system controls extinction of aversive memories. Export

@article{citeulike:570817, abstract = {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.}, address = {Molecular Genetics of Behaviour, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany.}, author = {Marsicano, G. and Wotjak, C. T. and Azad, S. C. and Bisogno, T. and Rammes, G. and Cascio, M. G. and Hermann, H. and Tang, J. and Hofmann, C. and Zieglg\"{a}nsberger, W. and Di Marzo, V. and Lutz, B.}, citeulike-article-id = {570817}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature00839}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12152079}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12152079}, day = {1}, doi = {10.1038/nature00839}, issn = {0028-0836}, journal = {Nature}, keywords = {behavior, cannabinoid}, month = {August}, number = {6897}, pages = {530--534}, posted-at = {2006-09-22 09:14:28}, priority = {0}, title = {The endogenous cannabinoid system controls extinction of aversive memories.}, url = {http://dx.doi.org/10.1038/nature00839}, volume = {418}, year = {2002} }

TY - JOUR ID - citeulike:570817 L3 - citeulike-article-id:570817 N2 - 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. IS - 6897 JF - Nature SN - 0028-0836 AD - Molecular Genetics of Behaviour, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. EP - 534 TI - The endogenous cannabinoid system controls extinction of aversive memories. VL - 418 SP - 530 KW - behavior KW - cannabinoid AU - Marsicano, G AU - Wotjak, CT AU - Azad, SC AU - Bisogno, T AU - Rammes, G AU - Cascio, MG AU - Hermann, H AU - Tang, J AU - Hofmann, C AU - Zieglgänsberger, W AU - Di Marzo, V AU - Lutz, B PY - 2002/08/01/ UR - http://dx.doi.org/10.1038/nature00839 ER -