Adolescent THC Exposure Changed Gene Networks in Mouse Brains Differently by Sex
In mice exposed to high-dose THC during early adolescence, gene expression changes linked to cognitive deficits varied by sex and brain region, with female changes concentrated in the striatum and males in the nucleus accumbens.
Quick Facts
What This Study Found
THC-treated mice showed memory and social behavior changes in late adolescence. Gene coexpression analysis identified "cognitive modules" that correlated with both THC treatment and memory deficits. In females, these modules related to endocannabinoid signaling in the dorsal striatum and inflammation in the ventral tegmental area. In males, they related to synaptic transmission in the nucleus accumbens. Four shared key driver genes (Hapln4, Kcnc1, Elavl2, Zcchc12) were linked to human cannabis use disorder vulnerability.
Key Numbers
High-dose THC during early adolescence; 5 brain regions profiled; cognitive modules identified in female dorsal striatum, female VTA, and male NAc; 4 shared key driver genes (Hapln4, Kcnc1, Elavl2, Zcchc12) linked to human CUD
How They Did This
Female and male C57BL6/N mice treated with high-dose THC during early adolescence (equivalent to heavy human use). Memory and social behaviors assessed in late adolescence. Transcriptomes profiled in five brain regions. Gene coexpression network analysis identified modules correlating with THC and cognition. Key drivers compared to human CUD genetic data.
Why This Research Matters
This study reveals that THC may affect male and female brains through fundamentally different molecular pathways, which could explain why cannabis use disorder presents differently by sex. The identification of shared key driver genes bridges animal and human findings.
The Bigger Picture
Sex differences in cannabis effects have been observed clinically but poorly understood mechanistically. This study provides a molecular framework showing the brain responds to adolescent THC differently depending on sex, which could eventually inform sex-specific prevention and treatment strategies.
What This Study Doesn't Tell Us
Mouse model using high-dose THC during a specific developmental window. Human adolescent cannabis use involves different doses, frequencies, and durations. Gene expression changes in mice may not directly map to human brain responses. Only one dose level tested.
Questions This Raises
- ?Would lower THC doses produce the same sex-specific patterns?
- ?Do the four shared key driver genes represent viable drug targets?
- ?Do human adolescents show similar sex-specific brain changes with cannabis use?
Trust & Context
- Key Stat:
- 4 key driver genes shared with human CUD
- Evidence Grade:
- Sophisticated multi-region transcriptomic analysis with human genetic cross-reference, but animal model with high doses limits direct human application
- Study Age:
- 2022 study
- Original Title:
- Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions.
- Published In:
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(12), 2071-2080 (2022)
- Authors:
- Zuo, Yanning(2), Iemolo, Attilio(3), Montilla-Perez, Patricia(3), Li, Hai-Ri, Yang, Xia, Telese, Francesca
- Database ID:
- RTHC-04340
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Does cannabis affect boys' and girls' brains differently?
In this mouse study, yes. THC during adolescence altered different gene networks in different brain regions depending on sex. Females showed changes in the striatum and reward areas, while males showed changes in the nucleus accumbens.
Were any findings relevant to humans?
Four key driver genes identified in the mouse study were also associated with genetic susceptibility to cannabis use disorder in humans, suggesting shared biological mechanisms across species.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-04340APA
Zuo, Yanning; Iemolo, Attilio; Montilla-Perez, Patricia; Li, Hai-Ri; Yang, Xia; Telese, Francesca. (2022). Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(12), 2071-2080. https://doi.org/10.1038/s41386-022-01413-2
MLA
Zuo, Yanning, et al. "Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions.." Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. https://doi.org/10.1038/s41386-022-01413-2
RethinkTHC
RethinkTHC Research Database. "Chronic adolescent exposure to cannabis in mice leads to sex..." RTHC-04340. Retrieved from https://rethinkthc.com/research/zuo-2022-chronic-adolescent-exposure-to
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.