title: Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism.
abstract: The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), is the preferred drug for Parkinson's disease, but long-term treatment results in the drug-induced dyskinesias and other side effects. This study was undertaken to examine whether melatonin could potentiate low dose L-DOPA effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental parkinsonism. Mice were treated with the parkinsonian neurotoxin, MPTP, and different doses of melatonin and low doses of L-DOPA. Behavior, striatal histology, and dopamine metabolism were evaluated on the 7th day. MPTP-induced striatal dopamine loss was not modified by melatonin administration (10-30 mg/kg; i.p. at 10-hr intervals, 6 times; or at 2-hr intervals, by day). However, low doses of L-DOPA (5 mg/kg, by oral gavage) administered alone or along with melatonin (10 mg/kg, i.p.) twice everyday for 2 days, 10 hr apart, after two doses of MPTP significantly attenuated striatal dopamine loss and provided improvements in both catalepsy and akinesia. Additionally, Golgi-impregnated striatal sections showed preservation of the medium spiny neurons, which have been damaged in MPTP-treated mouse. The results demonstrated that melatonin, but not L-DOPA, restored spine density and spine morphology of medium spiny neurons in the striatum and suggest that melatonin could be an ideal adjuvant to L-DOPA therapy in Parkinson's disease, and by the use of this neurohormone, it is possible to bring down the therapeutic doses of L-DOPA.
authors: Division of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
authors: Amit
authors: A
authors: Naskar
authors: Thamilarasan
authors: T
authors: Manivasagam
authors: Joy
authors: J
authors: Chakraborty
authors: Raghavendra
authors: R
authors: Singh
authors: Bobby
authors: B
authors: Thomas
authors: Muralikrishnan
authors: M
authors: Dhanasekaran
authors: Kochupurackal P
authors: KP
authors: Mohanakumar
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000819:agonists / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000819:agonists / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D003712:Dendrites / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007980:Levodopa / Q000819:agonists / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008550:Melatonin / Q000819:agonists / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000978:Antiparkinson Agents; D002492:Central Nervous System Depressants; D007980:Levodopa; D008550:Melatonin; D004298:Dopamine
keywords: L-DOPA; MPTP; behavior; dendritic spines; spine density