From Cloud Nine to Cognitive Decline: Nicotine's Impact on Adolescent Brains
Mia Wallace, played by Uma Thurman in the 1994 movie Pulp Fiction
Adolescence, often depicted as a rollercoaster ride of emotions and growth, holds many challenges for teenagers. From navigating mood swings to grappling with hormonal changes, it's a transformative phase both physically and emotionally. Recent studies shed light on how different parts of the brain mature at varying rates during adolescence. The limbic areas, responsible for motivation and reward, take the lead in development, while areas governing decision-making and self-control, like the prefrontal cortex, continue to evolve into early adulthood. This asynchronous development sets the stage for what many recognize as the impulsive nature of teenage behaviour. However, adolescence isn't just about emotional turbulence. It's also a time of increased risk for a range of issues, from mood disorders to risky behaviours like substance abuse. Among these, experimentation with drugs like nicotine emerges as a significant concern. Socially accepted and readily available, exposure to nicotine through smoking or vaping can exert a profound influence on the developing brain.
In their recent paper, the Addiction Research Group from Western University sought to determine how nicotine use during adolescence can impact cognition later in life. To do so, they used a rodent model for nicotine exposure and found that adolescent nicotine exposure affected male and female rodents differently. Males, in particular, showed a significantly higher susceptibility to cognitive deficits in adulthood following adolescent nicotine exposure. In contrast, the females did not show any signs of cognitive deficits.
The researchers measured cognition in adulthood through two tests: “temporal order novel object recognition” and sociability. Temporal order novel object recognition is a test that is used to measure temporal memory or the memory that is associated with the order in which events occur. This was measured through two exploration phases followed by a test phase. During the first exploration phase, the researchers placed the rat in an open area and let it explore two identical objects. In the next exploration phase, the rat was reintroduced to the same area, except both objects were swapped with another set of two identical objects. After exploring the objects in both phases, the rat was ready for the test phase! During this phase, the rat was p laced in the same arena one final time, except this time, there would be one copy of the old object (from the first phase) and one copy of the new object (from the second phase). Spending more time exploring the older object compared to the newer object indicated better temporal order recognition memory. Surprisingly, the researchers found that only the male rats exposed to nicotine during adolescence spent less time around the older object, indicating a memory impairment in males and not females in adulthood following adolescent nicotine exposure!
Next, they wanted to measure whether nicotine during adolescence affected social motivation in adulthood. To do this, they put the rodent in a large box with two sides on each side. One side had a stranger rat, and the other was empty. To measure social motivation, the researchers examined how long the test rat spent exploring the side with the stranger rat vs. the empty side. Notably, only male animals that were exposed to nicotine during adolescence showed less interest in the stranger rat, indicating reduced social motivation, while the females showed no significant decrease in social motivation.
Though these findings show behavioural and cognitive effects of adolescent nicotine exposure, the researchers wanted to learn more about the mechanism behind these behavioural differences in males vs. females. They analyzed the brain tissue of the rats using special techniques to look at the proteins involved in learning, memory, and social behaviour. They found that in male rats exposed to nicotine, there were significant decreases in proteins like acetylcholine and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex, a brain area important for controlling thoughts, actions, and emotions. These protein changes were not seen in female rats.
These findings show how nicotine can affect different populations. This research underscores the importance of understanding the cognitive impact of substances of abuse on both male and female adolescent brain development. By researching the effects of addictive drugs like nicotine, scientists hope to pave the way for targeted interventions and support systems to safeguard the well-being of all teenagers as they navigate the challenges of adolescence.
Original article: Ng, T; Sarikahya, M; Hudson, R; Szkudlarek, H; Valenzuela, E; Uzuneser, T; Proud, E, Gummerson, D; Youssef, M; Machado, M; Zhaksylyk, K; DeVuono, M; Chen, C; Yeung, K; Rushlow, W; Laviolette, S (2024). Adolescent Nicotine Exposure Induces Long-Term, Sex-Specific Disturbances in Mood and Anxiety-Related Behavioral, Neuronal and Molecular Phenotypes in the Mesocorticolimbic System. Neuropsychopharmacology. https://doi.org/10.1038/s41386-024-01853-y.