Lifespan changes in cannabinoid 1 receptor mRNA expression in the female C57BL/6J mouse brain

J Comp Neurol. 2023 Feb;531(2):294-313. doi: 10.1002/cne.25427. Epub 2022 Oct 14.


Many brain functions that underlie behavior, cognition, and emotions vary with age, as does susceptibility to neuropsychological disorders. The expression of specific genes that are involved in these functions, such as the genes encoding for oxytocin, its receptors, and apolipoprotein D, varies with age across different brain regions. The cannabinoid 1 receptor (CB1 R) is one of the most widely spread G-protein coupled receptors in the central nervous system and is increasingly recognized for its important contribution to various brain functions. Although changes in CB1 R expression with age have been reported in the male mouse brain, they have not been well investigated in the female brain. Here, we used fluorescence in situ hybridization to target CB1 R mRNA in the whole brains of female C57BL/6J mice aged 4, 6, 12, 52 (12 months) and 86 weeks (20 months), and quantified CB1 R-positive cells in 36 brain regions across the whole brain. The results showed that CB1 R-positive cells number changed with age. Specifically, CB1 R expression increased with age in some subregions of the cortex, decreased with age in the lateral septal area, and reached its lowest level at 52 weeks in the thalamus, hypothalamus, and hindbrain subregions. Cluster analysis revealed that some brain regions shared similar temporal characteristics in CB1 R-positive cell number across the lifespan. Our results provide evidence that investigation of the neural basis of age-related characteristics of female brain functions is not only warranted but required.

Keywords: cannabinoid 1 receptor; female brain; maturation and aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Cannabinoids* / metabolism
  • Female
  • In Situ Hybridization, Fluorescence
  • Longevity*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptors, Cannabinoid / metabolism


  • Receptors, Cannabinoid
  • RNA, Messenger
  • Cannabinoids
  • Receptor, Cannabinoid, CB1