Sex Differences in High Fat Diet‐Induced Enhanced Sensitivity to Methamphetamine and Dopamine D1 Receptor Agonist SKF 82958

Abstract

Eating a diet high in fat can lead to obesity and insulin resistance. Further, eating high fat laboratory chow enhances sensitivity of rats to the behavioral effects of drugs acting on dopamine systems (e.g., methamphetamine). For example, male rats eating high fat chow are more sensitive to the locomotor stimulating effects of methamphetamine than rats eating standard chow. The locomotor‐stimulating effects of methamphetamine are due, in part, to increased action of dopamine at dopamine D1 receptors; however, it is not known if diet enhances sensitivity of rats to the behavioral effects of dopamine D1 receptor agonists (e.g., SKF 82958). To test the hypothesis that eating a high fat diet enhances sensitivity rats to locomotion induced by dopaminergic drugs, male and female Sprague‐Dawley rats ate either standard (17% kcal from fat) or high fat (60% kcal from fat) chow and were tested once per week with SKF 82958 (0.01–3.2 mg/kg) or methamphetamine (0.1–3.2 mg/kg) using a cumulative dosing procedure for 6 weeks. Male and female rats eating high fat chow were more sensitive to the locomotor‐stimulating effects methamphetamine than control rats eating standard chow. Female rats eating high fat chow, but not males, were also more sensitive to the locomotor stimulating effects of SKF 82958 than female rats eating standard chow. Taken together with previous research, these results suggest that among females, eating high fat chow might impact sensitivity to methamphetamine via dopamine D1 receptor specific changes, while among males, high fat diet‐induced enhanced sensitivity to methamphetamine might be due to dopamine D2 receptor specific changes. Future experiments will examine differences in dopamine receptor expression among male and female rats eating different diets.Support or Funding InformationUTEP COURIThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.