Eating high fat chow and the behavioral effects of direct-acting and indirect-acting dopamine receptor agonists in female rats

Abstract

Eating high fat chow increases the sensitivity of male rats to some behavioral effects of the direct-acting dopamine receptor agonist quinpirole; it is not known whether sensitivity to quinpirole is similarly enhanced in female rats eating high fat chow. Female Sprague-Dawley rats had free access to standard chow (5.7% fat) or either free or restricted access (i.e. body weight matched to rats eating standard chow) to high fat (34.3% fat) chow. Quinpirole (0.0032-0.32 mg/kg) produced hypothermia and a low frequency of yawning. Eating high fat chow produced insulin resistance without affecting quinpirole-induced yawning or hypothermia. Pretreatment with the dopamine D2 receptor antagonist L-741,626 failed to increase quinpirole-induced yawning, indicating that the low frequency of yawning was not due to enhanced D2 receptor sensitivity. Compared with younger (postnatal day 75), drug-naive female rats in a previous study, rats in the present study (postnatal day 275) were more sensitive to cocaine-elicited (1-17.8 mg/kg) locomotion and the development of sensitization across 5 weeks; however, eating high fat chow did not further enhance these effects. These results suggest that drug history and age might modulate the effects of diet on sensitivity to drugs acting on dopamine systems.

Figure 1

Body weight of rats throughout the experiment. Baseline refers to the last of 4 weeks that all subjects (n = 30) had free access to standard chow (gray symbols). Thereafter rats had free access to standard chow (n = 10), free access to high fat chow (n = 10), or restricted access to high fat chow (n = 10; body weight was matched to rats eating standard chow). Quinpirole was tested alone once per week during weeks 1–7; quinpirole was tested in combination with different doses of L-741,626 during weeks 8–11; and cocaine was tested alone once per week during weeks 12–16. Insulin testing is indicated by arrows and occurred on days 10, 17 and 24. Vertical axis: body weight in g recorded at the end of each week. Horizontal axis: week in study.

Figure 2

Dose-response curves for quinpirole-induced yawning (upper panels) and quinpirole-induced changes in body temperature (lower panels) during week 1 (left panels) and week 7 (right panel) in rats with free access to standard chow, free access to high fat chow, or restricted access to high fat chow. Vertical axes: upper panels, mean (±SEM) yawns per 10 min; lower panels, body temperature in °C. Horizontal axes: dose of quinpirole in mg/kg body weight (V = vehicle).

Figure 3

Dose-response curves for quinpirole-induced yawning (upper panels) and quinpirole-induced changes in body temperature (lower panels) during weeks 8–11 in rats eating standard chow; quinpirole was studied alone and in combination with three different doses of L-741,626. Vertical axes: upper panel, mean (±SEM) yawns per 10 min; lower panel, body temperature in °C. Horizontal axes: dose of quinpirole in mg/kg body weight (V = vehicle).

Figure 4

Change in blood glucose concentration (mean ± SEM, milligrams per deciliter; vertical axis) determined after 10 days of free access to standard chow (n = 10), free access to high-fat chow (n = 10), or restricted access to high fat chow (n = 10). * = Significantly different from baseline (prior to insulin) blood glucose concentration.

Figure 5

Locomotor activity counts/5 min period after the administration of cocaine in female rats that had eaten standard or high fat chow for 12 or 16 weeks (upper and lower panels, respectively). Vertical axes: mean ± SEM locomotor activity counts / 5 min period. Horizontal axes: dose of cocaine in mg/kg body weight (V = vehicle).

Figure 6

AUC for cocaine dose-response curves determined once per week during weeks 12–16 in rats with free access to standard chow, free access to high fat chow, or restricted access to high fat chow. Vertical axis: mean (± SEM) AUC. Horizontal axis: week in study.