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Master of Science




Khokhar, Jibran Y.


Nicotine and cannabis are commonly co-used during adolescence, yet there is limited research on their long-lasting impacts on behavior and neural connectivity. This study examines the long-term effects of adolescent exposure to nicotine and high Δ9-tetrahydrocannabinol-cannabis (THC) flower vapor on brain development and reward-learning and seeking behavior. Male and female adolescent Sprague-Dawley rats received daily exposure to vaporized nicotine, THC, both nicotine and THC together, or vehicle vapor. In adulthood, behavioral tests and MRI scans were conducted. Female adult rats co-exposed to both nicotine and THC in adolescence demonstrated a heightened sensitivity to reward, while males exposed to THC displayed learning impairments. Males exposed to THC also expressed one network with increased functional connectivity compared to the co-exposed nicotine and THC group. Our results indicate that co-exposure to vaporized cannabis and nicotine during adolescence produces long-term sex-specific effects in reward- and cognition-related behavior.

Summary for Lay Audience

Nicotine and cannabis are commonly used substances by adolescents in Canada, with their dual use being on the rise among Canadian high school students in recent years. Limited research exists surrounding the consequences of nicotine and cannabis co-use in adolescence on subsequent behavior and brain development in adulthood. Evidence suggests that exposure to nicotine or cannabis in isolation during early stages of brain development, such as in adolescence, alters brain activity and behavioral and cognitive outcomes. However, the long-term outcomes of adolescent nicotine vapor and cannabis co-exposure remain unclear, and this lack of information may facilitate the continual use of both substances by adolescents under the guise of no harmful outcomes. Thus, this study aimed to characterize the long-term behavioral and neural effects of nicotine and cannabis vapor co-exposure using male and female adolescent rats. Adolescent rats were administered either nicotine vapor, cannabis vapor, both vapors, or air and vapor containing no active substances daily for 14 days. After reaching adulthood, exposed rats then underwent behavioral tests that explored reward learning and reinforcing behavior. We found that cannabis impaired reward-learning in males only; an effect that seemed to be neutralized by co-exposure to nicotine. We also found that the co-exposure of cannabis and nicotine in females induced hyper-reactivity to a new setting, which may be indicative of increased reward sensitivity. We then explored the effects of adolescent cannabis and nicotine exposure on adult brain activity. Brain activity was increased in a network involved in sensory processing, responsible for smell and hearing, in adult male rats exposed to cannabis, compared to males co-exposed to cannabis and nicotine. In contrast, females exhibited no alterations in brain network connectivity across groups. This study’s findings suggest that adolescent nicotine and cannabis exposure may lead to opposing or additive long-term behavioral and neural effects, which differ across sexes.