Effects of long-term administration of melatonin and a putative antagonist on the ageing rat

Adult rats were treated with either melatonin, the putative melatonin antagonist N-(2,4 dinitrophenyl)-5-meth- oxytryptamine (ML-23), their combination, or a vehicle for 16 months via the drinking water. The survival rates, serum testosterone and densities of ,¹²⁵I-melatonin binding sites in the medulla-pons and hypothalamus of the animals at the age of 27-29 months were significantly higher in the melatonin than vehicle-treated group. Surprisingly, ML-23 without or with melatonin, also prolonged the lifespan of the aged animals. ML-23 treatment greatly increased ¹²⁵I-melatonin binding in the medulla-pons whereas this increase was prevented by melatonin supplementation. Thus melatonin can attenuate age-related decrease in survival rates, testosterone and brain ¹²⁵I-mela- tonin binding sites, while chronic blockade by the putative antagonist also elicits melatonin-mimetic responses, perhaps by effecting supersensitivity.