EFFECTS OF LONG-TERM ADMINISTRATION OF MELATONIN AND A PUTATIVE ANTAGONIST ON THE AGING RAT

ADULT rats were treated with either melatonin, the putative melatonin antagonist N-(2,4 dinitrophenyl)-5-methoxytryptamine (ML-23), their co mbination, or a vehicle for 16 months via the drinking water. The surv ival rates, serum testosterone and densities of I-125-melatonin bindin g sites in the medulla-pons and hypothalamus of the animals at the age of 27-29 months were significantly higher in the melatonin than vehic le-treated group. Surprisingly, ML-23 without or with melatonin, also prolonged the lifespan of the aged animals. ML-23 treatment greatly in creased I-125-melatonin binding in the medulla-pons whereas this incre ase was prevented by melatonin supplementation. Thus melatonin can att enuate age-related decrease in survival rates, testosterone and brain I-125-melatonin binding sites, while chronic blockade by the putative antagonist also elicits melatonin-mimetic responses, perhaps by effect ing supersensitivity.