During the normal process of aging, production of melatonin decreases as well as alterations in dopaminergic function are known. The aim of this study was to assess the effects of chronic treatment with melatonin on central dopamine (DA) neurotransmitter and motor ability in aged rats. Accumulation of 3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a measure of tyrosine hydroxylation rate in vivo. Male aged Wistar rats received melatonin (1 mg/kg/day in drinking water with 1% alcohol to increase melatonin solubility, 4 weeks, n=6). Control young (3 months, n=6) and aged rats (20 months, n=6) also received 1% alcohol in drinking water, and were maintained under controlled conditions (22ordm;C, 70% humidity, 12/12LD). Animals were evaluated for motor ability and balance by using rota-rod. The rats were given prior training sessions to acclimate them to apparatus. Rats were placed on the rotating rod and the length of time on the rod was taken as measure of competency. Each rat performed 5 separate trials and the results were averaged. After that, rats were sacrificed by decapitation and samples of striatum analyzed by HPLC with electrochemical detection to measure DOPA, DA and the metabolite homovanillic acid (HVA). Tyrosine hydroxylation decreased significantly in the striatum of aged rats (34%) respect to the young controls. In accordance, intraneuronal DA content and HVA metabolite were also reduced (55% and 33%, respectively), showing the impairment in dopamine neurotransmission with age. However, when aged rats were treated with melatonin, an important increase in tyrosine hydroxylation (44%), DA content (126%) and HVA (26%) were observed in the striatum. When control aged rats were tested using rota-rod impaired their skill and increased the number of falls compared to the young control group. However melatonin treatment resulted in significant improvement in fall off time as compared to control aged rats. In conclusion, the results indicate that repeated treatment with melatonin might aid to improve the descent in dopamine neurotransmission and motor ability that normally occurs as a consequence of aging.

Supported by SAF2007-66878-CO2-02 from MEC.