Rats eating high fat chow are more sensitive to the behavioral effects of dopaminergic drugs, including methamphetamine and the dopamine D2/D3 receptor agonist quinpirole, than rats eating standard chow. However, limited work has explored possible sex differences regarding the impact of diet on drug sensitivity. It is also unknown if eating high fat chow enhances sensitivity of rats to other dopamine (e.g., D1) receptor agonists. To explore these possibilities, male and female Sprague Dawley rats eating standard laboratory chow (17% kcal from fat) or high fat chow (60% kcal from fat) were tested once per week for 6 weeks with dopamine D1 receptor agonist SKF 82958 (0.01-3.2 mg/kg) or methamphetamine (0.1-3.2 mg/kg) using cumulative dosing procedures. Eating high fat chow increased sensitivity of male and female rats to methamphetamine-induced locomotion; however, only female rats eating high fat chow were more sensitive to SKF 82958-induced locomotion. SKF 82958-induced eye blinking was also marginally, though not significantly enhanced among female rats eating high fat chow, but not males. Further, while dopamine D2 receptor expression was significantly increased for SKF 82958-treated rats eating high fat chow regardless of sex, no differences were observed in dopamine D1 receptor expression. Taken together, the present study suggests that while eating high fat chow enhances sensitivity of both sexes to dopaminergic drugs, the mechanism driving this effect might be different for males versus females. These data further demonstrate the importance of studying both sexes simultaneously when investigating factors that influence drug sensitivity.

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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.