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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

On Disruption of Fear Memory by Reconsolidation Blockade: Evidence from Cannabidiol Treatment

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Author(s):
Stern, Cristina A. J. ; Gazarini, Lucas ; Takahashi, Reinaldo N. ; Guimaraes, Francisco S. [1] ; Bertoglio, Leandro J. [2]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Dept Pharmacol, BR-14049 Ribeirao Preto, SP - Brazil
[2] Univ Fed Santa Catarina, Dept Farmacol, CCB, BR-88049900 Florianopolis, SC - Brazil
Total Affiliations: 2
Document type: Journal article
Source: NEUROPSYCHOPHARMACOLOGY; v. 37, n. 9, p. 2132-2142, AUG 2012.
Web of Science Citations: 62
Abstract

The search for reconsolidation blockers may uncover clinically relevant drugs for disrupting memories of significant stressful life experiences, such as those underlying the posttraumatic stress disorder. Considering the safety of systemically administered cannabidiol (CBD), the major non-psychotomimetic component of Cannabis sativa, to animals and humans, the present study sought to investigate whether and how this phytocannabinoid (3-30 mg/kg intraperitoneally; i.p.) could mitigate an established memory, by blockade of its reconsolidation, evaluated in a contextual fear-conditioning paradigm in rats. We report that CBD is able to disrupt 1- and 7-days-old memories when administered immediately, but not 6 h, after their retrieval for 3 min, with the dose of 10 mg/kg being the most effective. This effect persists in either case for at least 1 week, but is prevented when memory reactivation was omitted, or when the cannabinoid type-1 receptors were antagonized selectively with AM251 (1.0 mg/kg). Pretreatment with the serotonin type-1A receptor antagonist WAY100635, however, failed to block CBD effects. These results highlight that recent and older fear memories are equally vulnerable to disruption induced by CBD through reconsolidation blockade, with a consequent long-lasting relief in contextual fear-induced freezing. Importantly, this CBD effect is dependent on memory reactivation, restricted to time window of <6h, and is possibly dependent on cannabinoid type-1 receptor-mediated signaling mechanisms. We also observed that the fear memories disrupted by CBD treatment do not show reinstatement or spontaneous recovery over 22 days. These findings support the view that reconsolidation blockade, rather than facilitated extinction, accounts for the aforementioned CBD results in our experimental conditions. Neuropsychopharmacology (2012) 37, 2132-2142; doi:10.1038/npp.2012.63; published online 2 May 2012 (AU)

FAPESP's process: 07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders
Grantee:Francisco Silveira Guimaraes
Support Opportunities: Research Projects - Thematic Grants