Fatty Acid Amide Hydrolase and Cannabinoid Receptor Type 1 Genes Regulation is Modulated by Social Isolation in Rats

Neurochem Res. 2024 May;49(5):1278-1290. doi: 10.1007/s11064-024-04117-9. Epub 2024 Feb 18.


Social isolation is a state of lack of social connections, involving the modulation of different molecular signalling cascades and associated with high risk of mental health issues. To investigate if and how gene expression is modulated by social experience at the central level, we analyzed the effects of 5 weeks of social isolation in rats focusing on endocannabinoid system genes transcription in key brain regions involved in emotional control. We observed selective reduction in mRNA levels for fatty acid amide hydrolase (Faah) and cannabinoid receptor type 1 (Cnr1) genes in the amygdala complex and of Cnr1 in the prefrontal cortex of socially isolated rats when compared to controls, and these changes appear to be partially driven by trimethylation of Lysine 27 and acetylation of Lysine 9 at Histone 3. The alterations of Cnr1 transcriptional regulation result also directly correlated with those of oxytocin receptor gene. We here suggest that to counteract the effects of SI, it is of relevance to restore the endocannabinoid system homeostasis via the use of environmental triggers able to revert those epigenetic mechanisms accounting for the alterations observed.

Keywords: Endocannabinoid system; Endocannabinoid-Oxytocinergic systems interplay; Epigenetics; Rats; Social isolation.

MeSH terms

  • Amidohydrolases* / genetics
  • Animals
  • Endocannabinoids* / metabolism
  • Lysine*
  • Rats
  • Receptor, Cannabinoid, CB1* / genetics
  • Receptors, Cannabinoid / metabolism
  • Social Isolation*


  • Amidohydrolases
  • Endocannabinoids
  • fatty-acid amide hydrolase
  • Lysine
  • Receptor, Cannabinoid, CB1
  • Receptors, Cannabinoid