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

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.

Electrophysiological Effects of Repeated Administration of Agomelatine on the Dopamine, Norepinephrine, and Serotonin Systems in the Rat Brain

“…This is mainly because of the fact that it decreased both the number of bursts and the firing rate of VTA-DA neurons. The involvement of melatonin in the control of DA transmission is in line with data showing that a chronic treatment with melatonin alone induces an increase in the tissular level of DA in old rats (Esteban et al, 2010). Further experiments are necessary to determine whether melatonin by itself can induce a modification of the discharge pattern of VTA-DA neurons.…”

The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats

“…It is well known that antioxidants are potent scavengers of free oxygen radicals and serve as inhibitors of oxidative stress [1]. Melatonin (Mel), a multifunctional indolamine, is released from the pineal gland [20]. Recent studies revealed that Mel and its receptors are present in the pancreas, whereas its production is independent from the pineal gland [41].…”

Melatonin protection from chronic, low-level ionizing radiation

“…This has been amply documented in studies where melatonin was shown to protect against tissue damage and cellular death resulting from free radicals generated as a result of processes that either involve exposure to radioactivity or other toxins that stimulate free radical production. Thus, melatonin has been repeatedly shown to reduce free radical-mediated damage in the gastrointestinal tract [87], lungs [68], liver [69,88], kidney [89], testis [54], urinary bladder [90], pancreas [91], bone marrow [92], brain [38,93] and spinal cord [20], skeletal muscle [19], and other organs as well. These ubiquitous actions of melatonin show that its distribution in the body is not limited to only some organs.…”