Eating a ketogenic diet enhances sensitivity of rats to the effects of methamphetamine, but not dopamine D2/D3 receptor agonist quinpirole

Abstract

High fat diets are linked to several negative health consequences in humans including disrupted insulin signaling, and research with rodents has demonstrated that these diets can also increase individual sensitivity to drugs that act on dopamine systems. Since ketogenic diets have different effects on weight and insulin signaling than traditional high fat diets, it was hypothesized that a ketogenic diet (high in fat but very low in carbohydrates) might not increase sensitivity of rats to dopaminergic drugs. To test this hypothesis rats eating standard chow (17 % kcal from fat), high fat chow (60 % kcal from fat), or ketogenic chow (90.5 % kal from fat) were tested once weekly with quinpirole [0.0032–0.32 mg/kg, intraperitoneally (i.p.)] or methamphetamine (0.1–3.2 mg/kg, i.p.) using a cumulative dosing procedure. Consistent with previous reports, eating high fat chow enhanced sensitivity of rats to the behavioral effects of quinpirole and methamphetamine. While eating a ketogenic chow did not impact sensitivity to quinpirole, rats eating ketogenic chow were more sensitive than rats eating standard chow to methamphetamine-induced locomotion, but only at the largest cumulative dose tested. These results suggest that traditional high fat diets and ketogenic diets might produce similar, but non-identical effects on sensitivity to the behavioral effects of dopaminergic drugs.