Melanin-concentrating hormone does not modulate serotonin release in primary cultures of fetal raphe nucleus neurons |
| |
Institution: | 1. Departamento de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;2. Departamento de Neurofarmacología Experimental, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay;3. Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay;1. Department of Neurology and Division of Otolaryngology and Dentistry, Department of Surgery, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Avenue, Toledo, OH 43614, United States;2. Chief of Geriatrics, Extended Care and Rehabilitation, Atlanta VA Healthcare System, and Assistant Professor of Neurology, Emory University, Atlanta, GA (Formerly Sharon Shannon-Hartman);3. Department of Anatomy, Oral Roberts University, Tulsa, OK, United States;1. Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, China;2. The Central Laboratory, The First Hospital, Lanzhou University, 1 Donggang West Road, Lanzhou 730000, China;3. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, China;2. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran |
| |
Abstract: | Melanin-concentrating hormone (MCH) is a neuropeptide present in neurons located in the hypothalamus that densely innervate serotonergic cells in the dorsal raphe nucleus (DRN). MCH administration into the DRN induces a depressive-like effect through a serotonergic mechanism. To further understand the interaction between MCH and serotonin, we used primary cultured serotonergic neurons to evaluate the effect of MCH on serotonergic release and metabolism by HPLC-ED measurement of serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels. We confirmed the presence of serotonergic neurons in the E14 rat rhombencephalon by immunohistochemistry and showed for the first time evidence of MCHergic fibers reaching the area. Cultures obtained from rhombencephalic tissue presented 2.2 ± 0.7% of serotonergic and 48.9 ± 5.4% of GABAergic neurons. Despite the low concentration of serotonergic neurons, we were able to measure basal cellular and extracellular levels of 5-HT and 5-HIAA without the addition of any serotonergic-enhancer drug. As expected, 5-HT release was calcium-dependent and induced by depolarization. 5-HT extracellular levels were significantly increased by incubation with serotonin reuptake inhibitors (citalopram and nortriptyline) and a monoamine-oxidase inhibitor (clorgyline), and were not significantly modified by a 5-HT1A autoreceptor agonist (8-OHDPAT). Even though serotonergic cells responded as expected to these pharmacological treatments, MCH did not induce significant modifications of 5-HT and 5-HIAA extracellular levels in the cultures. Despite this unexpected result, we consider that assessment of 5-HT and 5-HIAA levels in primary serotonergic cultures may be an adequate approach to study the effect of other drugs and modulators on serotonin release, uptake and turnover. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|