Vaporizing Adolescence: Determining the Neurobiological Consequences of Adolescent Vaping on the Prefrontal Cortex, Nucleus Accumbens, and Ventral Tegmental Area

Abstract ID 94045 Poster Board 121 Electronic nicotine delivery systems (ENDS) are distinctly different from combustible cigarettes due to the availability of flavor options. This key difference has contributed to a high degree of popularity among adolescent and teen populations. To date, there have been no preclinical investigations into the impact of vaporized nicotine on late-developing brain regions such as the prefrontal cortex. The goal of this investigation was to determine how neuronal function and drug self-administration differed between adult and adolescent exposure timepoints. Male and female adolescent (7 weeks old) and adult (3 months old) C57BL/6J mice were used in a e-Vape® self-administration (EVSA) assay. Self-administration occurred overed a 20 session paradigm where 5 sessions were fixed-ratio 1, 5 sessions at FR2, 5 sessions at FR3, 3 sessions on a progressive ratio, and 2 final sessions at FR3. Following this, brains were extracted for brain slice patch-clamp electrophysiology. Sections containing the ventral tegmental area (VTA) and were collected to determine changes in intrinsic excitability in VTA dopamine neurons. Additional sections were collected to examine pyramidal cells in the prelimbic area of the medial prefrontal cortex (mPFC). Finally, sections containing the nucleus accumbens (NAc) were prepared to examine changes in dopamine release via fast-scan cyclic voltammetry. We observed that adolescent and adult mice self-administered nicotine plus menthol with similar magnitudes of reinforcement-related behaviors. We observed that adults and adolescents also exhibited similar changes in VTA dopamine neuron excitability. However, we observed that adolescent mice exhibited a significant increase in intrinsic excitability (lower rheobase and increased firing frequency) of mPFC pyramidal neurons when compared to adult mice. Additionally, the magnitude of reinforcement-related behavior observed during EVSA assays correlated with adolescent mPFC neuronal excitability; but did not with adult mPFC neuronal excitability. Electrically-evoked dopamine in the NAc core was observed to be greater in adolescent mice when compared to adult mice. These observations show that adolescent exposure may uniquely change the prelimbic area of the mPFC. The established correlation between self-administration and mPFC neuronal excitability in adolescent mice suggests a causal role in drug intake and may suggest this brain region to be uniquely important for adolescent nicotine dependence. Given the importance of this brain region, this suggests early exposure to vaporized nicotine may trigger other long-term consequences, included increased abuse liability to nicotine and other drugs. This work was supported by NIDA (DA050717 to BJH).