Eating high fat chow, but not drinking sucrose or saccharin, enhances the development of sensitization to the locomotor effects of cocaine in adolescent female rats.

Eating high fat chow accelerates the development of sensitization to cocaine-induced locomotion in female rats. It is not known whether consumption of sucrose or saccharin also increases sensitivity to the behavioral effects of cocaine or whether continuous (or intermittent) access to these feeding conditions is necessary to change sensitivity. Adolescent female Sprague-Dawley rats were assigned to one of seven feeding conditions from postnatal day 25 through to postnatal day 60. The rats either ate high fat (60% kcal from fat) chow and drank water or ate standard (17% kcal from fat) chow and drank either water, a 10% sucrose solution, or a 0.1% saccharin solution. The rats either had continuous access to high fat chow, sucrose, or saccharin, or had intermittent access (i.e. 2 days/week) to these substances, with access to water and standard chow on other days. As compared with standard chow, continuous (but not intermittent) access to high fat chow enhanced the development of sensitization to cocaine-induced (1-17.8 mg/kg) locomotion; drinking sucrose or saccharin (continuous or intermittent access) did not alter the development of sensitization to cocaine-induced locomotion. The impact of feeding condition on the behavioral effects of cocaine varies between sexes and across dietary composition.

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

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.

Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning.

Diet can impact sensitivity of rats to some of the behavioral effects of drugs acting on dopamine systems. The current study tested whether continuous access to sucrose is necessary to increase yawning induced by the dopamine receptor agonist quinpirole, or if intermittent access is sufficient. These studies also tested whether sensitivity to quinpirole-induced yawning increases in rats drinking the non-caloric sweetener saccharin. Dose-response curves (0.0032-0.32 mg/kg) for quinpirole-induced yawning were determined once weekly in rats with free access to standard chow and either continuous access to water, 10% sucrose solution, or 0.1% saccharin solution, or intermittent access to sucrose or saccharin (i.e., 2 days per week with access to water on other days). Cumulative doses of quinpirole increased then decreased yawning, resulting in an inverted U-shaped dose-response curve. Continuous or intermittent access to sucrose enhanced sensitivity to quinpirole-induced yawning. Continuous, but not intermittent, access to saccharin also enhanced sensitivity to quinpirole-induced yawning. In all groups, pretreatment with the selective D3 receptor antagonist PG01037 shifted the ascending limb of the quinpirole dose-response curve to the right, while pretreatment with the selective D2 receptor antagonist L-741,626 shifted the descending limb to the right. These results suggest that even intermittent consumption of diets containing highly palatable substances (e.g. sucrose) alters sensitivity to drugs acting on dopamine systems in a manner that could be important in vulnerability to abuse drugs.