title: Selective toxicity of L-DOPA to dopamine transporter-expressing neurons and locomotor behavior in zebrafish larvae.
abstract: Dopamine signaling is conserved across all animal species and has been implicated in the disease process of many neurological disorders, including Parkinson's disease (PD). The primary neuropathology in PD involves the death of dopaminergic cells in the substantia nigra (SN), an anatomical region of the brain implicated in dopamine production and voluntary motor control. Increasing evidence suggests that the neurotransmitter dopamine may have a neurotoxic metabolic product (DOPAL) that selectively damages dopaminergic cells. This study was designed to test this theory of oxidative damage in an animal model of Parkinson's disease, using a transgenic strain of zebrafish with fluorescent labeling of cells that express the dopamine transporter. The pretectum and ventral diencephalon exhibited reductions in cell numbers due to L-DOPA treatment while reticulospinal neurons that do not express the DAT were unaffected, and this was partially rescued by monoamine oxidase inhibition. Consistent with the MPTP model of PD in zebrafish larvae, spontaneous locomotor behavior in L-DOPA treated animals was depressed following a 24-h recovery period, while visually-evoked startle response rates and latencies were unaffected.
authors.affiliation: Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States; University of Oregon, Eugene, Institute of Neuroscience, United States.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Stednitz
authors.affiliation: Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States.
authors.forename: Briana
authors.initials: B
authors.lastname: Freshner
authors.affiliation: Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States; University of Massachusetts, Boston, Department of Neuroscience, United States.
authors.forename: Samantha
authors.initials: S
authors.lastname: Shelton
authors.affiliation: Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States; University of California, San Diego, Eating Disorders Center for Treatment & Research, United States.
authors.forename: Tori
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States.
authors.forename: Donovan
authors.initials: D
authors.lastname: Black
authors.affiliation: Department of Psychology, Humboldt State University, 1 Harpst Street, Arcata, CA 95521, United States. Electronic address: ethan.gahtan@humboldt.edu.
authors.forename: Ethan
authors.initials: E
authors.lastname: Gahtan
mesh_terms: D000818:Animals; D004027:Diencephalon / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism*; D007980:Levodopa / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D066250:Pretectal Region / Q000187:drug effects / Q000378:metabolism; D015027:Zebrafish
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D007980:Levodopa
keywords: Dopamine transporter; L-DOPA; Monoamine oxidase; Neurotoxicity; Parkinson's; Zebrafish