Leptin increases striatal dopamine D2 receptor binding in leptin-deficient obese (ob/ob) mice.
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.
Pfaffly
Jennifer
J
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11790, USA.
Michaelides
Michael
M
Wang
Gene-Jack
GJ
Pessin
Jeffrey E
JE
Volkow
Nora D
ND
Thanos
Panayotis K
PK
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D002421:Caudate Nucleus / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005838:Genotype; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009714:Nucleus Accumbens / Q000378:metabolism*; D010641:Phenotype; D011699:Putamen / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone; D014316:Tritium; D015431:Weight Loss / Q000502:physiology
D007328:Insulin; D020738:Leptin; D017448:Receptors, Dopamine D2; D014316:Tritium; D013134:Spiperone