title: Nasal administration of leptin dose-dependently increases dopamine and serotonin outflow in the rat nucleus accumbens.
abstract: Leptin is an anorexigenic hormone that acts via its receptor (LepR) to regulate the hypothalamic arcuate nucleus circuitry to mediate energy homeostasis and feeding behavior. Moreover, leptin decreases the reward value of natural and artificial rewards, and low levels of circulating leptin have been implicated in several mood disorders linking leptin to the mesolimbic system. Therefore, the purpose of this study was to assess whether and to what extent an acute intranasal application of leptin is able to modulate monoamine neurotransmitters in the nucleus accumbens (NAc). Microdialysis experiments were carried out in freely moving Wistar rats and in LepR-deficient Zucker rats (LepRfa/fa). Samples were analysed for the levels of dopamine (DA), serotonin (5-HT), and their metabolites using high-performance liquid chromatography with electrochemical detection. We show that in Wistar rats, nasal application of leptin dose-dependently increased extracellular DA and 5-HT levels in the NAc. By contrast, in the LepRfa/farats, nasal application of 0.12 mg/kg leptin failed to increase levels of either DA or 5-HT, but their metabolites (DOPAC and HIAA, respectively) were significantly decreased. In addition, leptin interaction with the melanocortin system was tested. Nasal co-administration of leptin and the melanocortin receptor antagonist, SHU9119, completely abolished the leptin-induced increase of both DA and 5-HT outflow in the NAc. These results indicate a marked leptin effect on the basal ganglia-related reward system involving melanocortin receptors.
authors.affiliation: Department of Neurology, Center of Brain, Behavior and Metabolism, Neurochemical Research Group, University of Lübeck, Lübeck, Germany. sonya.neto@neuro.uni-luebeck.de.
authors.forename: Sonya
authors.identifier: 0000-0002-4675-2940
authors.initials: S
authors.lastname: Neto
authors.affiliation: Department of Neurology, Center of Brain, Behavior and Metabolism, Neurochemical Research Group, University of Lübeck, Lübeck, Germany.
authors.forename: Ramya
authors.initials: R
authors.lastname: Varatharajan
authors.affiliation: Department of Neurology, Center of Brain, Behavior and Metabolism, Neurochemical Research Group, University of Lübeck, Lübeck, Germany.|Neuropharmacology Section, Department of Neurosurgery, University of Freiburg, Freiburg, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Joseph
authors.affiliation: Department of Neurology, Center of Brain, Behavior and Metabolism, Neurochemical Research Group, University of Lübeck, Lübeck, Germany.|Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Moser
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D055647:Rats, Transgenic; D017208:Rats, Wistar; D011924:Rats, Zucker; D044101:Receptors, Melanocortin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
chemical_list: D020738:Leptin; D018377:Neurotransmitter Agents; D044101:Receptors, Melanocortin; D012701:Serotonin; D004298:Dopamine
keywords: Dopamine; Leptin; Melanocortin; Nasal administration; Nucleus accumbens; Serotonin