title: Cannabinoid CB1 receptor mediates fear extinction via habituation-like processes.
abstract: 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.
authors.affiliation: Neuronal Plasticity/Mouse Behavior Group, Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Kamprath
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Jianrong
authors.initials: J
authors.lastname: Tang
authors.forename: Krisztina
authors.initials: K
authors.lastname: Monory
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Carsten T
authors.initials: CT
authors.lastname: Wotjak
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal; D003213:Conditioning, Psychological; D005072:Evoked Potentials, Auditory / Q000235:genetics / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear; D006185:Habituation, Psychophysiologic / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors
chemical_list: D043884:Receptor, Cannabinoid, CB1