A high-fat diet has sex-specific effects on nicotine vapor self-administration in mice

Abstract

BackgroundPrevious investigations have shown that fat-rich diets increase vulnerability to drug dependence, including nicotine. Despite this knowledge, few investigations into the neurochemical mechanisms have been completed. Our objective here was to examine if high-fat diet (HFD) impacted nicotine intake and in parallel examine potential changes in dopamine signaling. MethodsAdult male and female C57/BL6J mice were used in nicotine e-vape® self-administration (EVSA) assays after being maintained on a standard diet or HFD for 6 weeks. In a separate cohort of mice, dopamine release in the nucleus accumbens core was examined with fast-scan cyclic voltammetry. ResultsFemale mice assigned to HFD exhibited increased nicotine EVSA during low-effort responding (FR1) when compared to standard-diet mice. HFD-assigned mice (male and female) also exhibited reduced active nose pokes in a progressive ratio task. Finally, HFD-mice exhibited reduced phasic dopamine release compared to standard-diet mice. ConclusionsThese show that fat-rich diets alter nicotine intake (females increase at low effort, males and females decrease at high effort) and this may occur due to HFD-induced decreases in NAc dopamine release.