Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use

Paolo Taurisano, Linda A. Antonucci, Leonardo Fazio, Antonio Rampino, Raffaella Romano, Annamaria Porcelli, Rita Masellis, Marco Colizzi, Tiziana Quarto, Silvia Torretta, Annabella Di Giorgio, Giulio Pergola, Alessandro Bertolino, Giuseppe Blasi

Research output: Contribution to journalArticle

Abstract

The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively. Here, our aim was to use fMRI to investigate in healthy humans whether these SNPs interact in modulating prefrontal activity during working memory processing and if this modulation is linked with cannabis use. We recruited 242 healthy subjects genotyped for CNR1 rs1406977 and PTGS2 rs20417 that performed the N-back working memory task during fMRI and were interviewed using the Cannabis Experience Questionnaire (CEQ). We found that the interaction between CNR1 rs1406977 and PTGS2 rs20417 is associated with dorsolateral prefrontal cortex (DLPFC) activity such that specific genotype configurations (CNR1 C carriers/PTGS2 C carriers and CNR1 TT/PTGS2 GG) predict lower cortical response versus others in spite of similar behavioral accuracy. Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users. These results suggest that a genetically modulated balancing of signaling within the CB1-COX-2 pathway may reflect on more or less efficient patterns of prefrontal activity during working memory. Frequency of cannabis use may be a factor for further modulation of CNR1/PTGS2-mediated cortical processing associated with this cognitive process.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalCortex
Volume81
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • Cannabis
  • CB1
  • COX2
  • DLPFC
  • Working memory

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience

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  • Cite this

    Taurisano, P., Antonucci, L. A., Fazio, L., Rampino, A., Romano, R., Porcelli, A., Masellis, R., Colizzi, M., Quarto, T., Torretta, S., Di Giorgio, A., Pergola, G., Bertolino, A., & Blasi, G. (2016). Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use. Cortex, 81, 231-238. https://doi.org/10.1016/j.cortex.2016.05.010