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The effect of unilateral neurotoxic lesions to serotonin fibres in the medial forebrain bundle on the metabolism of [3H]DOPA in the telencephalon of the living rat
Institution:1. Neuroelectrophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;2. Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand;3. Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;4. Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand;1. Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, Japan;2. Department of Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata, Okayama, Japan;3. Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, Japan;4. Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, Japan;5. Department of Translational Research & Drug Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata, Okayama, Japan;1. CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;2. CIBB—Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal;3. IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal;4. Laboratory of Physiology—Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Abstract:We used quantitative autoradiography to measure the contribution of the 5-hydroxytryptamine (5-HT, serotonin) innervation of rat telencephalon to the synthesis of dopamine (DA) from exogenous l-DOPA. One week after stereotaxic infusions of 5,7-dihydroxytryptamine (5,7-DHT, 1.6 μg) into the right medial forebrain bundle (MFB), rats received 3H]DOPA (200 μCi, i.v.), which circulated for 90 min. The specific bindings in vitro of the 5-HT uptake site ligand 3H]citalopram and the DA uptake site ligand 125I]RTI-55 were measured in cryostat sections from the prosencephalon. In most structures ipsilateral to the lesion, 3H]citalopram specific binding was substantially reduced (50–90%). In the lateral habenula specific binding declined by only 30–40%, reflecting the presence of a 5-HT pathway deviating from the MFB at the mesencephalic flexure. 125I]RTI-55 binding in the basal ganglia was reduced by 50% on the side of the 5,7-DHT lesion, but was unperturbed in rats pretreated with desmethylimipramine (DMI). 5,7-DHT infusions decreased the synthesis of 3H]DA from 3H]DOPA in vivo in the basal ganglia by (40–90%). Pretreatment with DMI protected 3H]DA synthesis in the basal ganglia, but not in the olfactory tubercle and amygdala ipsilateral to the lesion. Whereas the 5-HT innervation does not contribute greatly to 3H]DA synthesis in the basal ganglia, a substantial proportion of 3H]DA synthesis in olfactory tubercle and amygdala requires an intact 5-HT innervation.
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