title: Melanin-concentrating hormone projections to the dorsal raphe nucleus: An immunofluorescence and in vivo microdialysis study.
abstract: Melanin-concentrating hormone (MCH)-containing neurons are localized in the lateral hypothalamus and incerto-hypothalamic areas, and project to several brain regions including the dorsal raphe nucleus (DRN). The MCHergic system has been involved in the regulation of emotional states and we have demonstrated that MCH microinjections into the rat DRN promote a depressive-like state. To understand the MCHergic transmission into the DRN, in the present study we characterized the distribution and density of the MCHergic fibers along the rostro-caudal axis of the rat DRN and their anatomical relationship with the 5-HT- and GABA-containing neurons. Additionally, a functional in vivo microdialysis study was carried out in order to evaluate the MCH effects on the 5-HT extracellular levels. Immunolabeling studies showed that MCHergic fibers were widely distributed throughout the rostro-caudal DRN extent and a reduced density at the most caudal level was observed. Interestingly, MCHergic fibers appeared in close apposition to 5-HT and GABA-containing neurons. Microdialysis studies evidenced an opposite effect of two concentrations of MCH on 5-HT levels: the lower concentration (30 μM) produced a significant and long-lasting (up to 120 min) decrease while the higher (100 μM) induced a slight and brief (20 min) increase. Morphological and functional results strongly suggest that both 5-HT- and GABA-containing neurons of the DRN are modulated by MCH. A different sensitivity of these neurons to MCH may explain the dose-response effect on 5-HT release. The decrease in extracellular 5-HT levels may account for the depressive-like effect induced by MCH reported in our previous studies.
authors.affiliation: Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Jessika
authors.initials: J
authors.lastname: Urbanavicius
authors.affiliation: Laboratorio de Neurotransmisión Peptídica, Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lagos
authors.affiliation: Laboratorio de Neurobiología del Sueño, Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Pablo
authors.initials: P
authors.lastname: Torterolo
authors.affiliation: Plataforma de Servicios Analíticos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Abin-Carriquiry
authors.affiliation: Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. Electronic address: scorzacecilia@gmail.com.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Scorza
mesh_terms: D000818:Animals; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D059330:GABAergic Neurons / Q000378:metabolism*; D007028:Hypothalamic Hormones / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008543:Melanins / Q000378:metabolism* / Q000494:pharmacology; D017551:Microdialysis; D009412:Nerve Fibers / Q000378:metabolism; D010907:Pituitary Hormones / Q000378:metabolism* / Q000494:pharmacology; D017208:Rats, Wistar; D059326:Serotonergic Neurons / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; C019463:melanin-concentrating hormone
keywords: 5-HT; Depression; GABA; Immunofluorescence; Microdialysis in vivo