title: Desensitization of leptin receptors is coincident with the upregulation of dopamine-related genes in the prefrontal cortex of adolescent mice.
abstract: We have investigated in adolescent mice the effect of subchronic leptin on (i) leptin receptor expression and functionality, and (ii) dopamine-related gene expression (tyrosine hydroxylase, Th; dopamine type-1 receptor, Drd1; dopamine type-2 receptor, Drd2) within the prefrontal cortex (PFC), which is involved in sensory perception of food and reward sensitivity, and the hippocampus, a brain area sensitive to food composition and pivotal in learning and memory processes related to feeding behaviour. Here, we show that leptin treatment triggered leptin resistance both in the hippocampus and in the PFC. In contrast, leptin induced the upregulation of dopamine-related genes in the PFC, whereas it failed to modify the expression of these genes in the hippocampus. The effect of leptin was similar irrespective of the time elapsed since the last leptin administration (either 2 or 14 h), indicating that the effect detected was not associated with leptin withdrawal. Our data show that leptin receptor desensitization is coincident with the upregulation of dopamine-related genes in the PFC of adolescent mice undergoing hyperleptinaemia triggered by exogenous leptin.
authors.affiliation: Department of Health and Pharmaceutical Sciences, School of Pharmacy, CEU-San Pablo University, Madrid, Spain.
authors.forename: Danila
authors.initials: D
authors.lastname: Del Rio
authors.forename: Nuria
authors.initials: N
authors.lastname: Del Olmo
authors.forename: Mariano
authors.initials: M
authors.lastname: Ruiz-Gayo
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000235:genetics*; D004435:Eating / Q000187:drug effects; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000235:genetics; D054411:Receptors, Leptin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D015854:Up-Regulation
chemical_list: D020738:Leptin; D011954:Receptors, Dopamine; D054411:Receptors, Leptin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine