Adolescent Nicotine Exposure Induces Dysregulation of Mesocorticolimbic Activity States and Depressive and Anxiety-like Prefrontal Cortical Molecular Phenotypes Persisting into Adulthood

Abstract

Considerable evidence demonstrates strong comorbidity between nicotine dependence and mood and anxiety disorders. Nevertheless, the neurobiological mechanisms linking adolescent nicotine exposure to mood and anxiety disorders are not known. Disturbances in the mesocorticolimbic dopamine (DA) system, comprising the prefrontal cortex (PFC), ventral tegmental area (VTA), and nucleus accumbens (NAc), are correlates of mood and anxiety-related symptoms and this circuitry is strongly influenced by acute or chronic nicotine exposure. Using a combination of behavioral pharmacology, in vivo neuronal electrophysiology and molecular analyses, we examined and compared the effects of chronic nicotine exposure in rats during adolescence versus adulthood to characterize the mechanisms by which adolescent nicotine may selectively confer increased risk of developing mood and anxiety-related symptoms in later life. We report that exposure to nicotine, selectively during adolescence, induces profound and long-lasting neuronal, molecular and behavioral disturbances involving PFC DA D1R and downstream extracellular-signal-related kinase 1-2 (ERK 1-2) signaling. Remarkably, adolescent nicotine induced a persistent state of hyperactive DA activity in the ventral tegmental area (VTA) concomitant with hyperactive neuronal activity states in the PFC. Our findings identify several unique neuronal and molecular biomarkers that may serve as functional risk mechanisms for the long-lasting neuropsychiatric effects of adolescent smoking behaviors.

Adolescent Cannabinoid and Nicotine Exposure Differentially Alters Adult Nicotine Self-Administration in Males and Females

“…Our findings suggest that adolescent cannabinoid exposure most likely alters the function of the mesolimbic pathway, as differences were found primarily on the ascending limb of the dose response function. In support of this notion, adolescent cannabinoid or nicotine exposure has previously been shown to alter monoaminergic signaling [37][38][39][40] . However, in our study, nicotine alone was ineffective in altering later drug taking behaviors in males, either in combination with the cannabinoid or alone.…”

The relationship between nicotine and psychosis

“…In a recent study, Jobson and colleagues used a rodent model of adolescent neurodevelopment to show that exposure to nicotine during a critical period of adolescent neurodevelopment led to long-term behavioural, neuronal and molecular phenotypes consistent with mood and anxiety-related disorders, including an alteration in neuronal activity states in both dopaminergic neuronal populations in the mesolimbic VTA, and increased spontaneous neural activity in the PFC. 28 This suggests a convergence of nicotine-induced neuroadaptation in the mesocorticolimbic system, leading to neuropsychiatric phenotypes which persist into adulthood, and has implications for the development of pharmacological interventions to prevent or reverse the long-term effects of nicotine exposure, as well as in identifying those who may be at increased risk from nicotine exposure during select periods of neurodevelopment.…”

<p>Anxiety and depression in women with and without chronic pelvic pain: prevalence and associated factors</p>

“…In the cross-sectional Nord-Trøndelag Health Study (HUNT-2), conducted with 60,814 participants, a significant association was found between smoking and MADD (OR=1.82; 95%CI: 1.69–1.95) 33. Some authors investigated the effect of nicotine on the central nervous system 34. In animal models, exposure to nicotine in adolescence was associated with anxiety- and depression-like behaviors due to the persistent state of hyperactive dopamine activity in the ventral tegmental area concomitant with hyperactive neuronal activity states in the prefrontal cortex 34.…”

“…Some authors investigated the effect of nicotine on the central nervous system 34. In animal models, exposure to nicotine in adolescence was associated with anxiety- and depression-like behaviors due to the persistent state of hyperactive dopamine activity in the ventral tegmental area concomitant with hyperactive neuronal activity states in the prefrontal cortex 34. In addition, smoking could be associated with MADD because this behavior is not very socially acceptable in Brazil, negatively affecting women’s self-esteem, as has already been reported in a different cultural setting 32…”