Repeated exposure to high-THC <i>Cannabis</i> smoke during gestation alters sex ratio, behavior, and amygdala gene expression of Sprague Dawley rat offspring
Bibliographic record
Abstract
Abstract Due to the recent legalization of Cannabis in many jurisdictions and the consistent trend of increasing THC content in Cannabis products, there is an urgent need to understand the impact of Cannabis use during pregnancy on fetal neurodevelopment and behavior. To this end, we repeatedly exposed female Sprague-Dawley rats to Cannabis smoke from gestational days 6 to 20 (n=12; Aphria Mohawk; 19.51% THC, <0.07% cannabidiol) or room-air as a control (n=10) using a commercially available system. Maternal reproductive parameters, behavior of the adult offspring, and gene expression in the offspring amygdala were assessed. Body temperature was decreased in dams following smoke exposure and more fecal boli were observed in the chambers before and after smoke exposure in those dams exposed to smoke. Maternal weight gain, food intake, gestational length, litter number, and litter weight were not altered by exposure to Cannabis smoke. A significant increase in the male-to-female ratio was noted in the Cannabis -exposed litters. In adulthood, both male and female Cannabis smoke-exposed offspring explored the inner zone of an open field significantly less than control offspring. Gestational Cannabis smoke exposure did not affect behavior on the elevated plus maze test or social interaction test in the offspring. Cannabis offspring were better at visual pairwise discrimination and reversal learning tasks conducted in touchscreen-equipped operant conditioning chambers. Analysis of gene expression in the adult amygdala using RNAseq revealed subtle changes in genes related to development, cellular function, and nervous system disease in a subset of the male offspring. These results demonstrate that repeated exposure to high-THC Cannabis smoke during gestation alters maternal physiological parameters, sex ratio, and anxiety-like behaviors in the adulthood offspring. Significance statement Cannabis use by pregnant women has increased alongside increased THC content in recent years. As smoking Cannabis is the most common method of use, we used a validated model of Cannabis smoke exposure to repeatedly expose pregnant rats to combusted high-THC Cannabis smoke. Our results show alterations in litter sex ratio, anxiety-like behavior, and decision making in the offspring which may relate to subtle changes in expression of amygdala genes related to development, cellular function, and nervous system disease. Thus, we believe this gestational Cannabis exposure model may be useful in delineating long-term effects on the offspring.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".