Grant: CIHR Fellowship

Smoking is arguably a developmental disease, with 70% of smokers starting before the age of 15. Smoking remains prevalent worldwide, with 20% of the population smoking regularly. Human neuroimaging studies have identified changes in connectivity between brain regions in smokers, however whether these differences are a result of smoking or reflect predispositional differences that helped initiate smoking require the use of animal models, which have a long history and utility in addiction research. Here, I will employ a preclinical model of adolescent nicotine exposure to study the longitudinal impacts of adolescent drug exposure on brain function and circuitry using neuroimaging together with behavioural testing. These measures will address whether adolescent exposure to nicotine produces a unique brain state, characterized by changes in neurotransmitter systems, connectivity and behaviours. The employed neuroimaging techniques will include functional magnetic resonance imaging (fMRI), to determine connectivity and network strength, and magnetic resonance spectroscopy (MRS). MRS quantifies brain metabolites, such as the main excitatory and inhibitory neurotransmitters, glutamate and ¿-aminobutyric acid (GABA) respectively, which show extensive developmental changes throughout the adolescent period. Once the developmental consequences of adolescent nicotine exposure have been quantified, I will implement a technique for viral delivery of designer receptors exclusively activated by designer drugs (DREADDs) to specifically target glutamatergic and GABAergic neural populations to determine the causal role of these neurotransmitter systems in this disease state. This research proposal offers an opportunity, unique to animal studies, to understand the longitudinal impact and preceding mechanism of adolescent nicotine exposure on brain circuitry and function. It will contribute to our understanding of adolescent development and its vulnerability to early drug exposure.