RT Journal Article SR Electronic T1 The effects of eating a high fat diet on sensitivity of male and female rats to methamphetamine and dopamine D1 receptor agonist SKF 82958 JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.119.263293 DO 10.1124/jpet.119.263293 A1 Jeremiah Ramos A1 Ethan J. Hardin A1 Alice H. Grant A1 Grace Flores-Robles A1 Adrian T. Gonzalez A1 Bryan Cruz A1 Arantxa K. Martinez A1 Nina M. Beltran A1 Katherine M. Serafine YR 2020 UL http://jpet.aspetjournals.org/content/early/2020/04/07/jpet.119.263293.abstract AB 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.SIGNIFICANCE STATEMENT While it is known that diet can impact sensitivity to some dopaminergic drugs, sex differences regarding this effect are not well characterized. This report demonstrates a robust sex difference regarding high fat diet-induced enhancement in drug sensitivity to dopaminergic drugs and suggests that the mechanism driving these changes in drug sensitivity might be different between sexes.