RT Journal Article
SR Electronic
T1 Cannabinoid CB1 Receptor Mediates Fear Extinction via Habituation-Like Processes
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6677
OP 6686
DO 10.1523/JNEUROSCI.0153-06.2006
VO 26
IS 25
A1 Kornelia Kamprath
A1 Giovanni Marsicano
A1 Jianrong Tang
A1 Krisztina Monory
A1 Tiziana Bisogno
A1 Vincenzo Di Marzo
A1 Beat Lutz
A1 Carsten T. Wotjak
YR 2006
UL http://www.jneurosci.org/content/26/25/6677.abstract
AB The interplay between fear expression and fear extinction provides an important prerequisite for adequate coping with aversive encounters. Current models propose that extinction of conditioned fear is mediated by associative safety learning. Here, we demonstrate that the cannabinoid CB1 receptor, which is crucially involved in fear extinction, is dispensable for associative safety learning. In fact, our results indicate that CB1 mediates fear extinction primarily via habituation-like processes. CB1 null-mutant mice were severely impaired not only in extinction of the fear response to a tone after fear conditioning but also in habituation of the fear response to a tone after sensitization with an inescapable footshock. Surprisingly, long-term habituation was generally affected even in situations with proper short-term adaptation, suggesting the existence of two separated CB1-dependent effector systems for short- and long-term fear adaptation. Our findings underscore the importance of habituation as a determinant of fear extinction in mice and characterize the cannabinoid CB1 receptor as an essential molecular correlate of this process.