The effects of eating a high fat or a ketogenic diet on sensitivity of female rats to methamphetamine

Abstract

Eating a high fat diet leads to negative health consequences such as obesity, type 2 diabetes, and dysfunction to dopamine systems. For example, eating a high fat laboratory chow enhances the sensitivity of rats to the behavioral effects of drugs of abuse (i.e., methamphetamine). Previous research has focused on diets that are high in fat and carbohydrates but low in protein. In contrast, a ketogenic diet is high in fat, low in carbohydrates, and low in protein. Ketogenic diets have been used in humans for the treatment of epilepsy and have been investigated for weight loss. Preclinical studies suggest that rats eating a ketogenic laboratory chow are less sensitive to the locomotor effects of cocaine (e.g., stereotypy). Based on this previous literature, it was hypothesized that eating high fat chow would enhance sensitivity of rats to methamphetamine‐induced locomotion and sensitization; however, rats eating ketogenetic chow would not differ from rats eating standard chow. To test this hypothesis rats eating standard chow (17% kcal from fat, 58% kcal from carbohydrate, 25% kcal from protein), high fat chow (60% kcal from fat, 21% kcal from carbohydrate, 18% kcal from protein), or ketogenic chow (90.5% kcal from fat, 0.3% kcal from carbohydrate, 9.2% kcal from protein) were tested once weekly with cumulative doses of methamphetamine (0.1–3.2 mg/kg; i.p.). After 4 weeks, rats eating high fat chow were more sensitive to the locomotor‐stimulating effects of smaller and intermediate doses of methamphetamine (e.g., 0.32, 1.0 mg/kg) than rats eating standard chow. Rats eating ketogenic chow were also more sensitive than rats eating standard chow to the locomotor‐stimulating effects of methamphetamine, but only at the largest dose tested (3.2 mg/kg). Future research will investigate the mechanisms underlying the effects of diet on sensitivity of rats to methamphetamine‐induced locomotion and sensitization, as well as examine the impact of these and other diets on sensitivity of rats to the rewarding and reinforcing effects of drugs of abuse.Support or Funding InformationThe authors have no conflicts to disclose. This work was supported by the National Institutes of Health, through the National Institute of General Medical Sciences under linked award numbers RL5GM118969, TL4GM118971, and UL1GM118970 and award number R25GM069621. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.