Chronic melatonin treatment and its precursor L-tryptophan improve the monoaminergic neurotransmission and related behavior in the aged rat brain

Authors

  • Susana Esteban,

    1. Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain
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  • Celia Garau,

    1. Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain
    2. Department of Pharmaceutical Sciences, University of California, Irvine, USA
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  • Sara Aparicio,

    1. Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain
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  • David Moranta,

    1. Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain
    2. Fundación Caubet-Cimera, Hospital Joan March, Mallorca, Spain
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  • Pere Barceló,

    1. Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain
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  • Maria Antonia Fiol,

    1. Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain
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  • Rubén Rial

    1. Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Mallorca, Spain
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Address reprint requests to Dr. Susana Esteban, Laboratorio de Neurofisiología, Instituto Universitario de Investigación en Ciencias de la Salud, Universitat de les Iles Balears, Ctra. Valldemossa Km 7,5 E-07122 Palma de Mallorca, Spain.
E-mail: susana.esteban@uib.es

Abstract

Abstract:  Melatonin has an important role in the aging process as a potential drug to relieve oxidative damage, a likely cause of age-associated brain dysfunction. As age advances, the nocturnal production of melatonin decreases potentially causing physiological alterations. The present experiments were performed to study in vivo the effects of exogenously administered melatonin chronically on monoaminergic central neurotransmitters serotonin (5-HT), dopamine (DA) and norepinephrine (NE) and behavioral tests in old rats. The accumulation of 5-hydroxy-tryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a measure of the rate of tryptophan and tyrosine hydroxylation in rat brain. Also neurotransmitters 5-HT, DA and NE and some metabolites were quantified by HPLC. In control rats, an age-related decline was observed in neurochemical parameters. However, chronic administration of melatonin (1 mg/kg/day, diluted in drinking water, 4 wk) significantly reversed the age-induced deficits in all the monoaminergic neurotransmitters studied. Also, neurochemical parameters were analyzed after administration of melatonin biosynthesis precursor L-tryptophan (240 mg/kg/day, i.p., at night for 4 wk) revealing similar improvement effects to those induced by melatonin. Behavioral data corresponded well with the neurochemical findings since spatial memory test in radial-maze and motor coordination in rota-rod were significantly improved after chronic melatonin treatment. In conclusion, these in vivo findings suggest that melatonin and L-tryptophan treatments exert a long-term effect on the 5-HT, DA and NE neurotransmission by enhancing monoamine synthesis in aged rats, which might improve the age-dependent deficits in cognition and motor coordination.

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