Abstract
Nicotine is the primary pharmacologic component of tobacco, and its highly addictive nature is responsible for its widespread use and significant withdrawal effects that result in challenges to smoking cessation therapeutics. Nicotine addiction often begins in adolescence and this is at least partially attributed to the fact that adolescent brain is most susceptible to the neuro-inflammatory effects of nicotine. There is increasing evidence for the involvement of microglial cells, which are the brain's primary homeostatic sensor, in drug dependence and its associated behavioral manifestations particularly in the adolescent brain. A hallmark of neuro-inflammation is microglial activation and activation of microglia by nicotine during adolescent development, which may result in long-term addiction to nicotine. This non-systematic review examines multifactorial etiology of adolescent nicotine addiction, neurobiology of nicotine addiction and the potential mechanisms that underlie the effects of nicotine on inflammatory signaling in the microglia, understanding how nicotine affects the adolescent brain. We speculate, that modulating homeostatic balance in microglia, could have promising therapeutic potential in withdrawal, tolerance, and abstinence-related neural adaptations in nicotine addiction, in the adolescent brain. Further, we discuss nicotine addiction in the context of the sensitization-homeostasis model which provides a theoretical framework for addressing the potential role of microglial homeostasis in neural adaptations underlying nicotine abuse.
Highlights
Nicotine addiction is the leading cause of preventable death and disease worldwide
The nicotine induced changes to microglial activation is mediated via the nucleus accumbens (NAc) localized D2 receptors and CX3CL1 signaling cascade suggesting that nicotine can induces significant changes to adolescent brain and behavior, and that microglial activation is a critical to this regulation [149]
Future Pharmacotherapeutic Approaches to Treat Nicotine Addiction. Both the neurochemical and functional changes observed in adolescent brain regions are associated with dopamine modulation and the cerebral reward system, which are influenced by specific genes, suggesting that a genetic predisposition of the neural mechanisms is involved in the acquisition of dependence in nicotine addiction
Summary
Nicotine addiction is the leading cause of preventable death and disease worldwide. Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects and these effects of nicotine may be an important factor in vulnerability to Tobacco Use Disorder (TUD) and may contribute to difficulty in quitting smoking. A recent study that examined reuptake and relapse to tobacco use across a variety of tobacco products such as cigarettes, electronic nicotine delivery systems, cigars, hookah, and smokeless tobacco showed that for all the tobacco products reuptake occurred in 7.8% of adult previous users and 30.3% of adolescent previous users [27] These data affirm that preventive strategies should be designed early, so as to reduce, delay, or eliminate any youth access to cigarettes. Available cessation strategies include community interventions such as educational programs; anti-tobacco counter-advertising at the local, state, and national levels and curtailing access to tobacco via smoking bans at home and school and increased tobacco prices in combination with pharmacotherapy, all of which may be effective in decreasing tobacco use in adolescents. In order to develop more effective therapeutic interventions, it is essential to understand the pathophysiology of addiction and examine the adolescent neurobiology and the genetic predisposition that underlies the etiology of adolescent nicotine addiction
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