Sex Differences in High Fat Diet‐Induced Enhanced Sensitivity to the Locomotor Stimulating Effects of Methamphetamine and SKF 82958

Abstract

Eating a high fat diet can impact dopamine systems; the same systems that are targeted by drugs of abuse. Rats eating high fat laboratory chow are more sensitive to the behavioral effects of abused drugs, including methamphetamine. Most of the previous research investigating diet‐induced effects on drug sensitivity has used male rats, therefore it is not known if females eating high fat chow are also more sensitive to the behavioral (e.g., locomotor‐stimulating) effects of methamphetamine. Methamphetamine‐induced locomotion is mediated, in part, by dopamine D1 and D2 receptors. While several reports have examined diet‐induced effects on dopamine D2 receptor agonists, it is not known if eating high fat chow also enhances sensitivity of rats to dopamine D1 receptor agonists (e.g., SKF 82958). To test the hypothesis that eating high fat chow enhances sensitivity of male and female rats to drugs that act on dopamine systems, male and female Sprague‐Dawley rats eating either standard laboratory chow (17% kcal from fat) or high fat chow (60% kcal from fat) were tested once per week for 6 total weeks with SKF 82958 (0.01–3.2 mg/kg) or methamphetamine (0.1–3.2 mg/kg) using a cumulative dosing procedure. In an initial cohort of animals (n=3/group), eating high fat chow tended to enhance sensitivity of female rats to SKF 82958 and methamphetamine. This trend was less apparent among male rats eating different diets. Consistent with previous reports, females tended to be more sensitive than males to the behavioral effects of both drugs, regardless of diet. Taken together with previous reports, the present study demonstrates that robust sex differences regarding the behavioral effects of dopaminergic drugs warrant further investigation of both sexes to understand the impact of diet on drug sensitivity. Future research will examine the effects of diet on sensitivity to the reinforcing effects of methamphetamine, to further assess how diet might impact abuse vulnerability.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.