Influence of body weight and type of chow on the sensitivity of rats to the behavioral effects of the direct-acting dopamine-receptor agonist quinpirole

Abstract

Rationale Amount and type of food can alter dopamine systems and sensitivity to drugs acting on those systems. Objectives This study examined whether changes in body weight, food type, or both body weight and food type contribute to these effects. Methods Rats had free or restricted access (increasing, decreasing, or maintaining body weight) to standard (5.7% fat) or high fat (34.3%) chow. Results In rats gaining weight with restricted or free access to high fat chow, both limbs of the quinpirole yawning dose-response curve (0.0032–0.32 mg/kg) shifted leftward compared with rats eating standard chow. Restricting access to standard or high fat chow (maintaining or decreasing body weight) decreased or eliminated quinpirole-induced yawning; within one week of resuming free feeding, sensitivity to quinpirole was restored, although the descending limb of the dose-response curve was shifted leftward in rats eating high fat chow. These are not likely pharmacokinetic differences because quinpirole-induced hypothermia was not different among groups. PG01037 and L-741,626 antagonized the ascending and descending limbs of the quinpirole dose-response curve in rats eating high fat chow, indicating D3 and D2 receptor mediation, respectively. Rats eating high fat chow also developed insulin resistance. Conclusions These results show that amount and type of chow alter sensitivity to a direct-acting dopamine receptor agonist with the impact of each factor depending on whether body weight increases, decreases, or is maintained. These data demonstrate that feeding conditions, perhaps related to insulin and insulin sensitivity, profoundly impact the actions of drugs acting on dopamine systems.

Enhanced vulnerability to tobacco use in persons with diabetes: A behavioral and neurobiological framework

“…Thus, the STZ model represents a common method of inducing diabetes via disruptions in insulin signaling. The high-fat diet (HFD) model of diabetes resembles the etiology of type 2 diabetes as animals develop insulin resistance and hyperglycemia (Baladi et al, 2011;Woods et al, 2003b). The percent of fat in the diet and the duration of time on the diet regimen impact the development of insulin resistance.…”

“…The percent of fat in the diet and the duration of time on the diet regimen impact the development of insulin resistance. The HFD regimen has been employed using various parameters, including diets consisting of 30% and above in fat content by weight and different durations of exposure ranging from 4 weeks to 20 weeks (Baladi et al, 2011;Buettner et al, 2007). The length of diet exposure has been shown to predict whether the HFD regimen produces insulin resistance in rodents (Buettner et al, 2007).…”

Eating high fat chow enhances the locomotor-stimulating effects of cocaine in adolescent and adult female rats

“…It is clear that dietary factors (how much and what is eaten) can impact dopamine systems and the effects of drugs acting on those systems (e.g., Baladi et al 2011;Bell et al 1997;McGuire et al 2011;Stamp et al 2008). For example, female adult rats eating high fat chow show greater cocaineinduced stereotypy, compared to female adult rats eating standard chow (Shumsky et al 1997).…”

Sensitivity to apomorphine-induced yawning and hypothermia in rats eating standard or high-fat chow

“…For example, the dose-response curve for dopamine receptor agonist (e.g., quinpirole)-induced yawning is an inverted U-shape with the ascending and descending limbs of the curve being mediated by D3 and D2 receptors, respectively (Baladi et al 2010;Collins et al 2005). In rats eating high-fat chow, both limbs of the dose-response curve are shifted leftward; however, antagonism of quinpirole-induced yawning is not different between rats eating high-fat or standard chow , indicating that the shifts leftward in the former reflect increased sensitivity at D3 (ascending limb) and D2 (descending limb) receptors (Baladi and France 2009;Baladi et al 2010Baladi et al , 2011Collins et al 2005). Food restriction, on the other hand, decreases sensitivity to, or in some cases eliminates, dopamine receptor agonist-induced yawning as evidenced by a flattening of the inverted U-shaped dose-response curve; this flattening is thought to reflect a selective increase in sensitivity at D2 receptors (i.e., descending limb; Collins et al 2008;Sevak et al 2008).…”