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Adolescent Nicotine Vaping Produced Sex-Specific Alterations in Mood and Anxiety Pathophysiology in the Mesolimbic Circuit

Madeline Machado

Scholarship@Western (Western University), 2025

Abstract

Adolescence is a critical period of neurodevelopment, during which the brain is vulnerable to exogenous insults, like nicotine. With rising rates of adolescent nicotine vaping, understanding the long-term impacts is crucial. Previous research links adolescent nicotine exposure to increased anxiety and depressive-like behaviours, and neuronal dysregulation. However, most preclinical studies rely on injection models. This study addresses that limitation by using a nicotine inhalation model that closely mimics human use. Male and female Sprague-Dawley rats were exposed to 0mg/mL (vehicle), 20mg/mL, or 40mg/mL nicotine vapour for 10 minutes, 3 times daily, for 10 consecutive days from postnatal day (PND) 35-44. Emotional behaviours assessed in adulthood revealed reduced anxiety-like behaviours in nicotine-exposed males. In-vivo electrophysiology and molecular analyses of the nucleus accumbens (NAc) and basolateral amygdala (BLA) revealed significant alterations in excitatory and inhibitory activity in males and females. These findings offer insight into the long-term consequences of adolescent nicotine exposure.

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