Leptin increases striatal dopamine D2 receptor binding in leptin-deficient obese (ob/ob) mice

Abstract

Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [(3)H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

Figure 1. Mean (+SEM) Weight Gain Before and After Leptin Treatment

Mean (+SEM) daily body weight in ob/ob and wild-type mice before and after treatment with vehicle or leptin. (*) wt-veh and wt-le mice weighed significantly less than ob-veh and ob-le mice before treatment. (ˆ) wt-veh and wt-le mice weighed significantly less than ob-veh and ob-le mice after treatment. (∼) wt-le and ob-veh mice weighed significantly more post-treatment and ob-le mice weighed significantly less post-treatment.

Figure 2. Mean (+SEM) Food Intake During 8 Day Leptin Treatment

Mean (+SEM) daily food intake in ob/ob and wild-type mice during the treatment period. (*) ob-le mice showed significantly lower food intake compared to ob-veh mice.

Figure 3. Mean (+SEM) plasma Leptin

Mean (+SEM) plasma leptin concentrations in ob/ob and wild-type mice after treatment with vehicle or leptin. (*) wt-le mice had significantly greater plasma leptin levels than wt-veh mice. (ˆ) ob-le mice had significantly greater plasma leptin levels than ob-veh mice.

Figure 4. Mean (+SEM) plasma Insulin

Mean (+SEM) plasma insulin concentrations in ob/ob and wild-type mice after treatment with vehicle or leptin. (*) wt-veh mice had significantly lower plasma insulin levels than ob-veh mice (ˆ) ob-le mice had significantly lower plasma insulin levels than ob-veh mice.

Figure 5. Mean (+SEM) [³H] spiperone D2R binding in ob/ob and wild-type mice after treatment with leptin or vehicle

Mean (+SEM) [³H] spiperone D2R binding in ob/ob and wild-type mice in the CPu and NAc after treatment with vehicle or leptin. Statistically significant differences between are denoted by the (*) symbol and connector lines.