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-methoxytryptamine (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 life-span 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-melatonin binding sites, while chronic blockade by the putative antagonist also elicits melatonin-mimetic responses, perhaps by effecting supersensitivity.
Oaknin-Bendahan
S
S
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Anis
Y
Y
Nir
I
I
Zisapel
N
N
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011149:Pons / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D044094:Receptors, Melatonin; D015996:Survival Rate; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D044094:Receptors, Melatonin; C053008:ML 23; D008735:5-Methoxytryptamine; D013739:Testosterone; D008550:Melatonin