High‐fat diets increase nicotine self‐administration in male and female mice by impacting dopamine release in the nucleus accumbens core

Abstract

Prior investigations focused on the impact of high‐fat diet (HFD) on nicotine reward and reinforcement have indicated that HFD exposure increases reward‐related and reinforcement‐related behaviors associated with nicotine. However, there has been no investigation into how nicotine‐related behaviors may be altered by HFD. To investigate the potential mechanisms of HFD on nicotine addiction‐related behaviors, we exposed adult male and female mice to HFD or a regular diet (RD) for 6 weeks. Following this, we trained mice in a nicotine e‐vape® self‐administration (EVSA) paradigm. Here mice, were trained to self‐administer 6 mg/mL nicotine on a fixed‐ratio 1 (FR1), FR3 and progressive‐ratio schedules. Following behavioral assays we anesthetized the mice and extracted brains for ex‐vivo fast‐scan cyclic voltammetry (FSCV) assays. We observed that both male and female mice exhibited an increase in nicotine intake on the FR1 schedule but had the same intake of nicotine as RD mice on a FR3 schedule. We also observed that both male and female mice exhibited a significantly lower breakpoint when assessed on a progressive ratio. Using FSCV, we observed that HFD mice exhibited a significant decrease in dopamine release in the nucleus accumbens core when compared to RD mice at both tonic and phasic stimulation frequencies. These data support the fact that HFD promotes nicotine intake at low‐effort schedules (FR1) and this may be due to decreased baseline dopamine release in the nucleus accumbens core.