title: Short-term adaptation of conditioned fear responses through endocannabinoid signaling in the central amygdala.
abstract: The cannabinoid receptor type 1 (CB1) and the central nucleus of the amygdala (CeA) are both known to have crucial roles in the processing of fear and anxiety, whereby they appear to be especially involved in the control of fear states. However, in contrast to many other brain regions including the cortical subregions of the amygdala, the existence of CB1 in the CeA remains enigmatic. In this study we show that CB1 is expressed in the CeA of mice and that CB1 in the CeA mediates short-term synaptic plasticity, namely depolarization-induced suppression of excitation (DSE) and inhibition (DSI). Moreover, the CB1 antagonist AM251 increased both excitatory and inhibitory postsynaptic responses in CeA neurons. Local application of AM251 in the CeA in vivo resulted in an acutely increased fear response in an auditory fear conditioning paradigm. Upon application of AM251 in the basolateral nucleus of the amygdala (BLA) in an otherwise identical protocol, no such acute behavioral effects were detected, but CB1 blockade resulted in increased fear responses during tone exposures on the subsequent days. Moreover, we observed that the efficacy of DSE and DSI in the CeA was increased on the day following fear conditioning, indicating that a single tone-shock pairing resulted in changes in endocannabinoid signaling in the CeA. Taken together, our data show the existence of CB1 proteins in the CeA, and their critical role for ensuring short-term adaptation of responses to fearful events, thereby suggesting a potential therapeutic target to accompany habituation-based therapies of post-traumatic symptoms.
authors.affiliation: Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Kamprath
authors.forename: Hector
authors.initials: H
authors.lastname: Romo-Parra
authors.forename: Martin
authors.initials: M
authors.lastname: Häring
authors.forename: Stefano
authors.initials: S
authors.lastname: Gaburro
authors.forename: Michael
authors.initials: M
authors.lastname: Doengi
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000223:Adaptation, Psychological / Q000502:physiology*; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010721:Phosphinic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency; D011984:Sensory Receptor Cells / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D010880:Piperidines; D011412:Propanolamines; D011720:Pyrazoles; D011724:Pyridazines; D011810:Quinoxalines; D043884:Receptor, Cannabinoid, CB1; C085075:CGP 55845A; C103505:AM 251; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; C049853:gabazine; D014633:Valine