Molecular and neuronal mechanisms underlying the effects of adolescent nicotine exposure on anxiety and mood disorders.

Introduction:
This article provides an in-depth examination of the relationship between nicotine exposure during adolescence and the risk of developing mood and anxiety disorders later in life. The author discusses the vulnerability of the adolescent brain and the potential toxic effects of nicotine exposure during this critical period of development. The reader will learn about the current clinical and pre-clinical evidence on the effects of nicotine exposure during adolescence and the specific neuropsychiatric vulnerabilities that may be increased as a result.

Key Points:

* adolescence represents a critical period of brain development, with significant changes occurring at the synaptic, molecular, and anatomical levels.
* Nicotine exposure during adolescence is associated with increased risk of developing mood and anxiety disorders later in life.
* The adolescent brain is more susceptible to the dependence-producing effects of tobacco, and adolescents may develop tobacco dependence at substantially lower concentrations of nicotine and over shorter periods of time.
* Electronic cigarettes (E-cigarettes) have become a popular smoking and nicotine delivery system for both adult and adolescent populations, with a significant increase in adolescent use between 2017 and 2018.
* Pre-clinical and clinical studies have demonstrated a strong association between tobacco use and the presence of mood and anxiety-related disorders.
* Nicotine exposure during adolescence has been shown to cause profound molecular, neurophysiological, and anatomical changes in the mesocorticolimbic circuitry.
* Pharmacologically reversing nicotine-induced dysregulation of GSK-3 signaling directly in the Nac has been shown to reverse many of the anxiety and depressive-like behavioral phenotypes observed in later adulthood.

Main Message:
The article highlights the urgent need to better understand the neurobiological mechanisms underlying the increased risk of neuropsychiatric disorders following adolescent nicotine exposure. The confluence of intricate neural developmental processes, increased risk-taking behaviors, and lack of impulse control, represents a profound vulnerability to the potential toxic effects of nicotine exposure on adolescent brain development. Given the strong epidemiological evidence demonstrating that a majority of lifetime smokers initiate their tobacco habits during adolescence, there is an urgent need to more clearly understand the precise neurobiological effects of nicotine exposure during these critical neurodevelopmental windows.

Laviolette SR. Molecular and neuronal mechanisms underlying the effects of adolescent nicotine exposure on anxiety and mood disorders. Neuropharmacology. 2021;184:108411. doi:10.1016/j.neuropharm.2020.108411