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Updated: Nov 27, 2025
Administration of Δ9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice
Published on: August 1, 2025
Adolescent Δ9-Tetrahydrocannabinol Exposure Selectively Impairs Working Memory but Not Several Other mPFC-Mediated
Han-Ting Chen1,2, Ken Mackie1,2
1Department of Psychology and Brain Sciences, Indiana University, Bloomington, IN, United States.
Abstract:
As the frequency of cannabis use by 14-16-year-olds increases, it becomes increasingly important to understand the effect of cannabis on the developing central nervous system. Using mice as a model system, we treated adolescent (28 day old) C57BL6/J mice of both sexes for 3 weeks with 3 mg/kg tetrahydrocannabinol (THC). Starting a week after the last treatment, several cognitive behaviors were analyzed. Mice treated with THC as adolescents acquired proficiency in a working memory task more slowly than vehicle-treated mice. Working memory recall in both sexes of THC-treated mice was also deficient during increasing cognitive load compared to vehicle-treated mice. Our adolescent THC treatment did not strongly affect social preference, anxiety behaviors, or decision-making behaviors on the elevated T maze task. In summary, under the conditions of this study, adolescent THC treatment of mice markedly affected the establishment, and persistence of working memory, while having little effect on decision-making, social preference or anxiety behaviors. This study provides further support that adolescent THC affects specific behavioral domains.
Insights
Adolescent tetrahydrocannabinol (THC) exposure in mice impaired working memory establishment and recall. This cannabis exposure did not significantly alter anxiety, social behaviors, or decision-making in developing mice.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pharmacology
Background:
- Increasing cannabis use among adolescents (14-16 years old) necessitates understanding its impact on the developing central nervous system.
- The adolescent brain undergoes significant development, making it potentially vulnerable to the effects of psychoactive substances like tetrahydrocannabinol (THC).
Purpose of the Study:
- To investigate the long-term effects of adolescent tetrahydrocannabinol (THC) exposure on cognitive functions in a mouse model.
- To determine if adolescent THC exposure impacts specific behavioral domains, including working memory, social preference, anxiety, and decision-making.
Main Methods:
- Adolescent male and female C57BL6/J mice (28 days old) were treated with 3 mg/kg tetrahydrocannabinol (THC) or vehicle for 3 weeks.
- Cognitive behaviors, including working memory, social preference, anxiety, and decision-making, were assessed starting one week after the final THC treatment.
- Working memory was evaluated using tasks assessing acquisition and recall under increasing cognitive load.
Main Results:
- Adolescent THC-treated mice demonstrated slower acquisition of working memory tasks compared to controls.
- Both male and female THC-exposed mice exhibited deficits in working memory recall under increasing cognitive load.
- No significant effects of adolescent THC treatment were observed on social preference, anxiety-like behaviors, or decision-making in the elevated T maze task.
Conclusions:
- Adolescent exposure to tetrahydrocannabinol (THC) significantly impacts the establishment and persistence of working memory in mice.
- The findings suggest that adolescent THC exposure affects specific cognitive domains, particularly working memory, while having minimal influence on anxiety, social behaviors, or decision-making under the study's conditions.
- This research underscores the specific vulnerability of the developing brain's working memory systems to cannabis exposure.
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