2014 May 7. doi: 10.1038/npp.2014.103. [Epub ahead of print]
The CB1 Receptor Antagonist AM251 Impairs Reconsolidation of Pavlovian Fear Memory in the Rat Basolateral Amygdala.
We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilisation, but only when administered post-reactivation. URB597 produced a small, transient enhancement of memory restabilisation when administered post-reactivation. The amnestic effect of AM251 was rescued by co-administration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as post-traumatic stress disorder.Neuropsychopharmacology accepted article preview online, 07 May 2014; doi:10.1038/npp.2014.103.
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