High fat diet and food restriction differentially modify the behavioral effects of quinpirole and raclopride in rats

Abstract

Nutritional status can impact dopamine systems in a manner that might be important to understanding possible common neurobiological mechanisms that mediate abnormal compulsive food (e.g., obesity) and drug taking. Limiting food intake, for example, can increase sensitivity to the behavioral effects of indirect-acting dopamine receptor agonists. Much less is known regarding possible diet-induced changes in sensitivity to direct-acting dopamine receptor drugs. The present study investigated the effects of a high fat diet and of food restriction on sensitivity of rats to the behavioral effects of a direct-acting dopamine receptor agonist and a dopamine receptor antagonist. Free access to high fat chow increased sensitivity to quinpirole-induced yawning without changing sensitivity to raclopride-induced catalepsy or quinpirole-induced hypothermia. Food restriction (10 g/day) decreased sensitivity to quinpirole-induced yawning and raclopride-induced catalepsy without affecting sensitivity to quinpirole-induced hypothermia. Free access to a standard chow restored sensitivity to the behavioral effects of both drugs in rats that were previously food-restricted but not in rats that previously ate a high fat diet. These data confirm that food restriction can decrease sensitivity to behavioral effects of direct-acting dopamine receptor drugs, they provide evidence (i.e., no change in hypothermic effects) indicating that these changes are not due to pharmacokinetic mechanisms, and they provide initial evidence showing enhanced sensitivity to behavioral effects of dopamine receptor drugs in rats eating a high fat diet. These changes in sensitivity of dopamine systems could be relevant to understanding the impact of nutrition on therapeutic and recreational drug use.

Figure 1

Body weight of separate groups of rats with free access to a standard laboratory chow, free access to a high fat chow, or restricted access to a standard chow. The vertical dashed lines indicate 4 phases of the study as follows: week 1 (all rats had free access to a standard chow); weeks 1–5 (different groups of rats had free access to a standard chow [circles], free access to a high fat chow [squares], or restricted access [10 g/day] to a standard chow [triangles]); weeks 6–13 (all rats had free access to a standard chow); and weeks 14–16 (individual rats had access to the same feeding conditions as in weeks 1–5). Each symbol represents the mean ± S.E.M. of 8 rats. The symbol shape (e.g., square) refers to the same group of rats across the different phases of the study; symbol shading (e.g. filled) designates different feeding conditions within a group.

Figure 2

The effects of a high fat and food-restricted diet on quinpirole-induced yawning (left panel) and quinpirole-induced hypothermia (right panel). Each symbol represents the mean ± S.E.M. of 8 rats. The top panels represent week 1, the middle panels represent week 5, and the bottom panels represent week 7 of the study (see Fig. 1). The points above V indicate the effects obtained with vehicle. #, P<0.05 and *, P<0.001, compared with rats that had free access to a standard chow throughout the study at the corresponding dose of quinpirole.

Figure 3

The effects of a high fat and food-restricted diet on raclopride-induced catalepsy. Each symbol represents the mean ± S.E.M. of 8 rats. The top panel represents week -1, the middle panel represents week 5, and the bottom panel represents week 7 of the study (time line shown in Fig. 1). The points above V indicate the effects obtained with vehicle. *, P<0.001 compared with rats that had free access to a standard chow throughout the study at the corresponding dose of raclopride.