title: Melatonin attenuates the amphetamine-induced decrease in vesicular monoamine transporter-2 expression in postnatal rat striatum.
abstract: The vesicular monoamine transporter-2 (VMAT-2) is responsible for packaging intraneuronal dopamine into synaptic vesicles in preparation for synaptic release and is a critical regulator of cytoplasmic dopamine levels and dopaminergic function. It has long been recognized that VMAT-2 is also a critical mediator of amphetamine-induced dopamine release. Amphetamine-induced lesions during development have the potential to produce numerous permanent abnormalities in neural circuitry and function. Therefore, in the present study, we investigated the effects of amphetamine on the levels of VMAT-2, α-synuclein and phosphorylated tyrosine hydroxylase in the striatum of neonatal rats. We found that chronic amphetamine administration in postnatal rats produces dopaminergic deficits in the striatum, including decreases in the levels of VMAT-2 and phosphorylated tyrosine hydroxylase. In addition, an increase in α-synuclein expression was observed in the striatum of postnatal rats following chronic amphetamine treatment. Furthermore, we identified a role of (10mg/kg) melatonin, a methoxyindole released from the pineal gland, in attenuating the detrimental effects of amphetamine on dopaminergic neurons.
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom 73170, Thailand.
authors.forename: Sujira
authors.initials: S
authors.lastname: Mukda
authors.forename: Oranich
authors.initials: O
authors.lastname: Vimolratana
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
mesh_terms: D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D051844:alpha-Synuclein; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D008550:Melatonin; D004298:Dopamine