Melatonin enhances L-DOPA therapeutic effects, helps to reduce its dose, and protects dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced XXXX in @entity19 .

@entity304 @entity19 @entity910 @entity191 @entity8364
UNASSIGNED: L-3,4-dihydroxyphenylalanine (L-DOPA) reduces symptoms of @entity191 ( @entity191 ), but suffers from serious side effects on long-term use. Melatonin (10-30  mg/kg, 6  doses at 10  hr intervals) was investigated to potentiate L-DOPA therapeutic effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced @entity304 in @entity19 . Striatal tyrosine hydroxylase (TH) immunoreactivity, TH, and phosphorylated ser 40 TH (p-TH) protein levels were assayed on 7th day. Nigral TH-positive neurons stereology was conducted on serial sections 2.8  mm from bregma rostrally to 3.74  mm caudally. MPTP caused 39% and 58% decrease, respectively, in striatal fibers and TH protein levels, but 2.5-fold increase in p-TH levels. About 35% TH neurons were lost between 360 and 600   m from 940   m of the entire nigra analyzed, but no neurons were lost between 250   m rostrally and 220   m caudally. When L-DOPA in small doses (5-8  mg/kg) failed to affect MPTP-induced @entity910 or @entity8364 , co-administration of melatonin with L-DOPA attenuated these behaviors. Melatonin administration significantly attenuated MPTP-induced loss in striatal TH fibers (82%), TH (62%) and p-TH protein (100%) levels, and nigral neurons (87-100%). Melatonin failed to attenuate MPTP-induced striatal dopamine depletion. L-DOPA administration (5  mg/kg, once 40  min prior to sacrifice, p.o.) in MPTP- and melatonin-treated @entity19 caused significant increase in striatal dopamine (31%), as compared to L-DOPA and MPTP-treated @entity19 . This was equivalent to 8  mg/kg L-DOPA administration in @entity191 @entity19 . Therefore, prolonged, effective use of L-DOPA in @entity191 with lesser side effects could be achieved by treating with 60% lower doses of L-DOPA along with melatonin.
