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The Effects of Daily Docosahexaenoic Acid Administration on High Fat Chow‐Induced Enhanced Sensitivity to Dopaminergic Drugs

Eating a diet high in fat can lead to several negative health consequences, including obesity, type 2 diabetes and dopamine system dysfunction. For example, rats eating high fat laboratory chow are more sensitive to the behavioral effects of drugs acting on dopamine systems, including direct‐(e.g., quinpirole) and indirect‐acting (e.g., cocaine) dopamine receptor agonists. Dietary supplementation with omega‐3 fatty acids, such as fish oil, can successfully prevent and treat this high fat chow‐induced enhanced sensitivity to dopaminergic drugs. Fish oil contains two omega‐3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), therefore the relative contribution of each fatty acid to the beneficial effects of fish oil are not known. To test the hypothesis that daily injections of DHA will prevent high fat diet‐induced enhanced sensitivity to the behavioral effects of cocaine (1.0–17.8 mg/kg), adolescent female rats ate standard laboratory chow (17% kcal from fat), or high fat chow (60% kcal from fat) in combination with daily injections of DHA or vehicle. Eating high fat chow enhanced sensitivity of female rats to cocaine‐induced locomotion as compared to rats eating standard chow alone. That is, the cocaine‐induced locomotion dose‐response curve was shifted upward in rats eating high fat chow, as compared to rats eating standard chow. Daily injections of DHA did not prevent this effect. Rats receiving daily injections of DHA (regardless of type of chow) gained significantly more weight than rats eating standard chow alone or high fat chow alone. While these results might suggest that EPA, rather than DHA, is the likely omega‐3 fatty acid driving the aforementioned effects of fish oil, only one dose of DHA has been examined thus far. Future experiments will focus on examining different doses of DHA alone and in combination with various doses of EPA to determine the relative contribution of each omega‐3 fatty acid in mediating the beneficial effects of fish oil. These data add to a growing literature regarding the health benefits of fish oil and omega‐3 fatty acids.