Eating High Fat Chow Enhances Sensitivity of Adolescent Rats to the Behavioral Effects of the Dopamine D ₂ /D ₃ Receptor Agonist Quinpirole

Eating high fat chow increases sensitivity of rats to drugs that act indirectly on dopamine receptors (e.g., cocaine). This effect is greatest in female adolescent rats. Eating high fat chow also enhances sensitivity of adult male rats to the behavioral effects of drugs that act directly on dopamine receptors (e.g., the dopamine D 2 /D 3 receptor agonist quinpirole); however, it is not known if this effect is greater in adolescents. It is also not known if there are sex differences in this diet‐induced enhancement that mirror those previously demonstrated with cocaine. To test the hypothesis that females are more sensitive than males to the diet‐induced effects on quinpirole‐induced yawning, male and female Sprague‐Dawley rats (postnatal day 25) eating either standard laboratory chow (17% kcal from fat) or high fat chow (60% kcal from fat), were tested once per week with quinpirole (0.0032–0.32 mg/kg) for 8 weeks. Eating high fat chow increased sensitivity to the behavioral effects of quinpirole in male rats. Specifically, quinpirole induced more yawning in male rats eating high fat chow, (e.g., an increase in the maximal effect) as compared to standard chow fed controls. In comparison, female rats yawned significantly less than their male counterparts, and eating high fat chow did not increase the frequency of yawning. These data suggest that alternative behavioral assays should be considered to measure sensitivity to the behavioral effects of dopamine receptor agonists in female rats. For example, other directly observable behaviors, such as locomotion or rearing, might provide a way to measure drug sensitivity in female rats. These results further demonstrate the importance of studying drug sensitivity in both male and female subjects.