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.

Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases

“…Animals models of PD (including rotenone, 6-hydroxydopamine (6-OHDA), and MPTP) have shown a benefit on motor function from melatonin in many [86][87][88][89], although not all [90,91], studies. Similarly, many but not all have shown benefits on measures of substantia nigra tyrosine hydroxylase or striatal dopamine compared to those not treated with melatonin [86][87][88][89][90][91][92].…”

Therapeutical Implications of Melatonin in Alzheimer’s and Parkinson’s Diseases

“…Changes in levodoparelated motor complications may be related to changes in melatonin secretion pattern. L -DOPA-related motor complications occur in nearly half of the patients with PD on completion of the fi rst 5 years of treatment (Koller 1996 ), and as noted above, results on experimental parkinsonism in mice support the use of melatonin as an adjuvant to L -to bring down the therapeutic doses of L -DOPA in PD (Naskar et al 2013 ).…”

“…Therefore, efforts are in the vogue to reduce the intake or to compensate for the side effects of this drug. In a recent study undertaken to examine whether melatonin could potentiate the effect of a low dose of L -DOPA in MPTP-induced experimental parkinsonism in mice, melatonin, but not L -DOPA, restored spine density and spine morphology of medium spiny neurons in the striatum suggesting that melatonin could be an ideal adjuvant to L -DOPA therapy in PD, making it possible to bring down the therapeutic doses of L -DOPA (Naskar et al 2013 ).…”

Embryonic Stem Cells Derived Neuron Transplantation Recovery in Models of Parkinsonism in Relation to Severity of the Disorder in Rats

“…14,[16][17][18] There are several behavioral tests for animal models of PD that display the onset and progression of the disease. 19,20 Some of the well-established behavioral tests in unilaterally lesioned animal models of PD include amphetamine-or apomorphine-induced unilateral rotations, cylinder test, elevated body swing test, skilled-forelimb use test, beam balancing test, etc. [21][22][23] Amphetamine-or apomorphineinduced rotatory response is used extensively by others and us for validating the development of the disease in hemiparkinsonian models.…”