Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the behavioral effects of quinpirole

Abstract

Consuming a high fat diet can lead to many negative health consequences, such as obesity, insulin resistance, and enhanced sensitivity to drugs acting on dopamine systems. It has recently been demonstrated that dietary supplementation with fish oil, which is rich in omega-3 fatty acids, can prevent this high fat diet-induced enhanced sensitivity to dopaminergic drugs from developing. However, it is not known if fish oil supplementation can reverse this effect once it has already developed. In order to test the hypothesis that dietary supplementation with fish oil will reverse high fat diet-induced enhanced sensitivity to quinpirole, a dopamine D₂/D₃ receptor agonist, male Sprague-Dawley rats were fed either standard chow (17% kcal from fat), high fat chow (60% kcal from fat), standard chow or high fat chow supplemented with 20% (w/w) fish oil. Body weight, food consumption, and sensitivity to quinpirole-induced (0.0032–0.32 mg/kg) penile erections were examined throughout the course of the experiment. Eating high fat chow enhanced sensitivity of rats to quinpirole-induced penile erections (i.e., resulted in a leftward shift of the ascending limb of the dose-response curve). Dietary supplementation with fish oil successfully treated this effect, since dose-response curves were not different for rats eating standard chow and rats eating high fat chow with fish oil. These results suggest that in addition to preventing the negative health consequences of eating a high fat diet, fish oil can also reverse some of these consequences once they have developed.

Dietary supplementation with fish oil reverses high fat diet-induced enhanced sensitivity to the behavioral effects of quinpirole

“…Rats eating high fat chow weighed significantly more than rats in all other dietary groups, although all subjects gained weight throughout the study (see Figure 1A). Even though rats eating standard chow supplemented with fish oil gained less weight throughout the experiment than rats eating high fat chow, or high fat chow with fish oil, they consumed the most amount of kcal per day on average of any group (similar to what has been reported previously, Hernandez-Casner et al, 2017). Greater kcal intake does not correlate with greater body weight; therefore, it is possible that fish oil supplementation is impacting metabolism.…”

“…In previous reports, when fish oil was added directly to the high fat chow, rats never developed enhanced sensitivity to the behavioral effects of dopaminergic drugs (Hernandez-Casner et al, 2017;Serafine et al, 2016). In other words, dietary supplementation with fish oil prevented high fat chow-induced enhanced sensitivity to quinpirole (Hernandez-Casner et al, 2017).…”

“…Dietary supplementation with fish oil, which is rich in omega-3 polyunsaturated fatty acids, is successful in preventing some of the negative health consequences associated with eating a high fat diet (e.g., insulin resistance and obesity; Hainault et al, 1993). In previous reports, when fish oil was added directly to the high fat chow, rats never developed enhanced sensitivity to the behavioral effects of dopaminergic drugs (Hernandez-Casner et al, 2017;Serafine et al, 2016). In other words, dietary supplementation with fish oil prevented high fat chow-induced enhanced sensitivity to quinpirole (Hernandez-Casner et al, 2017).…”

The Effects of Eating a High Fat Diet on Sensitivity of Male and Female Rats to Methamphetamine and Dopamine D1 Receptor Agonist SKF 82958

“…One potential factor that might underly the discordant results in the literature regarding receptor expression changes is body weight itself. For example, it has been well demonstrated that eating a high fat diet produces changes to drug sensitivity, similar to those demonstrated in this report, even in the absence of changes to body weight (Ramos et al, 2019;Baladi et al, 2011;Hernandez-Casner et al, 2019). In contrast, many of the reports demonstrating changes in dopamine receptor expression also describe increases in body weight among animals eating a high fat diet (Johnson and Kenny, 2010;South and Huang, 2008;Konner et al, 2011).…”

“…Further, changes to dopamine D2 receptor binding has also been demonstrated among obese human patients (Tomasi and Volkow, 2013;Wang et al, 2001;de Weijer et al, 2011). Although the rats in the present experiments were not definable as obese by many recognized definitions, we have previously demonstrated that body fact composition can be altered even in the absence of changes to overall body weight (Hernandez-Casner et al, 2019). Future research will explore the possible factors involved in weight gain versus body fat distribution changes that might be occurring concurrent to changes in dopamine receptor expression and sensitivity.…”