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Eur Neuropsychopharmacol. 2015 Jun;25(6):958-65. doi: 10.1016/j.euroneuro.2015.02.001. Epub 2015 Feb 16.

Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption.

Author information

1
Department of Pharmacology, Federal University of Santa Catarina, Florianopolis, SC, Brazil.
2
Department of Neurology, Psychiatry and Medical Psychology, University of São Paulo, Ribeirao Preto, SP, Brazil.
3
Department of Biochemistry and Molecular Biology I, Complutense University, Madrid, Spain; Centro de Investigación Biomedica en red en Enfermedades Neurodegenerativas, Madrid, Spain.
4
Department of Pharmacology, University of São Paulo, Ribeirao Preto, SP, Brazil.
5
Department of Pharmacology, Federal University of Santa Catarina, Florianopolis, SC, Brazil. Electronic address: leandro.bertoglio@ufsc.br.

Abstract

Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology. It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when taken separately and/or in conjunction with CBD. The present study sought to investigate this matter at a preclinical level. We report that THC (0.3-10mg/kg, i.p.) was able to disrupt the reconsolidation of a contextual fear memory, resulting in reduced conditioned freezing expression for over 22 days. This effect was dependent on activation of cannabinoid type-1 receptors located in prelimbic subregion of the medial prefrontal cortex and on memory retrieval/reactivation. Since CBD may counteract the negative psychotropic effects induced by THC and has been shown to be a reconsolidation blocker, we then investigated and demonstrated that associating sub-effective doses of these two compounds was equally effective in attenuating fear memory maintenance in an additive fashion and in a dose ratio of 10 to 1, which contrasts with that commonly found in C. sativa recreational samples. Of note, neither THC alone nor CBD plus THC interfered with anxiety-related behaviors and locomotor activity, as assessed in the elevated plus-maze test, at a time point coinciding with that used to evaluate their effects on memory reconsolidation. Altogether, present findings suggest a potential therapeutic value of using THC and/or CBD to mitigate a dysfunctional aversive memory through reconsolidation disruption in post-traumatic stress disorder patients.

KEYWORDS:

CB1 receptor; Cannabidiol; Fear memory; Medial prefrontal cortex; Reconsolidation; Δ(9)-Tetrahydrocannabinol

PMID:
25799920
DOI:
10.1016/j.euroneuro.2015.02.001
[Indexed for MEDLINE]

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