Delta(9)-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption

作者：Stern Cristina A J; Gazarini Lucas; Vanvossen Ana C; Zuardi Antonio W; Galve Roperh Ismael; Guimaraes Francisco S; Takahashi Reinaldo N; Bertoglio Leandro J

来源：European Neuropsychopharmacology, 2015, 25(6): 958-965.

DOI：10.1016/j.euroneuro.2015.02.001

• Fear memory
• Delta(9)-Tetrahydrocanna-binol
• Cannabidiol
• Reconsolidation
• CB1 receptor
• Medial prefrontal cortex

Delta(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 (0.3-10 mg/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 blacker, 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.

• 出版日期2015-6