The role of Tetrahydrocannabinol in inducing disrupted signaling cascades, hippocampal atrophy and memory defects

J Chem Neuroanat. 2021 Apr:113:101943. doi: 10.1016/j.jchemneu.2021.101943. Epub 2021 Mar 6.

Abstract

Tetrahydrocannabinol (THC), a major psychoactive constituent of marijuana, can substantially change the function of several brain areas, leading to behavioral impairment including memory and learning dysfunction. Given the importance of hippocampus as one of the chief parts of the brain involved in memory processing, the present study seeks to investigate structural and histological alterations in hippocampus as well as behavioral defects provoked by THC treatment. Besides, using genome-wide sequencing, we adopted a pathway-based approach to discover dysregulated molecular pathways. Our results demonstrated remarkable hippocampal atrophy, and also interrupted memory function and long term potentiation (LTP) under THC exposure. We also detected several dysregulated signaling pathways involved in synaptic plasticity as well as cell-cell interaction in the hippocampus of THC-treated rats. Overall, the results indicate a potential correlation between disrupted signaling cascades, hippocampal atrophy and memory defects caused by THC treatment.

Keywords: Hippocampus; Neurodegeneration; RNA-seq; Tetrahydrocannabinol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrophy / metabolism
  • Atrophy / pathology
  • Avoidance Learning / drug effects
  • Dronabinol / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Male
  • Memory / drug effects*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*

Substances

  • Dronabinol