title: Neonatal onset of leptin signalling in dopamine neurones of the ventral tegmental area in the rat.
abstract: Leptin inhibits feeding by acting on hypothalamic and mesolimbic dopamine (DA) pathways involved in the homeostatic and hedonic control of energy balance. In the rodent, the neonatal period is characterised by high circulating leptin concentrations and an insensitivity to the anorectic effects of this hormone, suggesting that the modulation of these circuits by leptin is reduced during this period. The present study aimed to examine the onset of the functional ventral tegmental area (VTA) response to leptin during the neonatal period and to characterise the phenotype of leptin-responsive VTA neurones. On postnatal day (PND) 10 in pups insensitive to the anorectic effects of leptin and exclusively dependent on their mother for feeding, leptin administration failed to increase phosphorylated signal transducer of activation and transcription 3 (pSTAT3) and phosphorylated extracellular signal-regulated kinase (pERK)1/2 immunoreactivity in the midbrain. At the onset of independent feeding on PND16, leptin stimulated pSTAT3 production in the lateral parabrachial pigmented area of the midbrain, with a subset of these pSTAT3-positive neurones co-localising with tyrosine hydroxylase, a marker of DA neurones. Leptin did not increase pERK1/2 immunoreactivity in DA neurones on PND16. These results suggest that the insensitivity of PND10 pups to the anorectic effects of leptin might be mediated, at least in part, by a lack of signalling through the Janus kinase/STAT signalling pathway in VTA DA neurones in response to leptin before the onset of independent feeding.
authors.affiliation: Douglas Mental Health University Institute, Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Naef
authors.forename: E
authors.initials: E
authors.lastname: Gjerde
authors.forename: H
authors.initials: H
authors.lastname: Long
authors.forename: D
authors.initials: D
authors.lastname: Richard
authors.forename: C-D
authors.initials: CD
authors.lastname: Walker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D005260:Female; D020738:Leptin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D054411:Receptors, Leptin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D014446:Tyrosine 3-Monooxygenase; D048052:Mitogen-Activated Protein Kinase 3
keywords: dopamine; leptin; neonatal development; pERK1/2; pSTAT3; ventral tegmental area