Studies on the mechanism of action of the abortive effect of 6-hydroxydopamine in rats.
Administration of repeated large doses of 6-hydroxydopamine (6-OHDA)(100 mg/kg) to pregnant rats causes a 75% decrease in the litter size, which is accounted for a corresponding increase in the number of foetuses resorbed or stillborn. Guanethidine, which like 6-OHDA, causes a prolonged sympathectomy did not interfere with the course of the pregnancy nor did bethanidine which interferes with sympathetic transmission without causing ultrastructural damage. When 6-OHDA was given only prior to mating the abortive effect was no longer present, even though the concentration of noradrenaline in the peripheral sympathetic nerves was reduced for the entire duration of the pregnancy. The reported alpha-adrenoreceptor blocking effects of 6-OHDA are not exclusively responsible for the abortive effect, since injection of sympathectomised rats with phentolamine (10 mg/kg) had no abortive effect. There were normal concentrations of noradrenaline in the brains of pups born to mothers treated during pregnancy with 6-OHDA. Whether the same is true of those foetuses resorbed, remains unresolved. It seems likely that the abortive effect is not related to the depletion of noradrenaline but is due to other effects of 6-OHDA.
D000019:Abortifacient Agents; D000818:Animals; D001627:Bethanidine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000187:drug effects; D005313:Fetal Death / Q000139:chemically induced; D005327:Fetal Resorption / Q000139:chemically induced; D006145:Guanethidine / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology*; D008098:Litter Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000019:Abortifacient Agents; D002395:Catecholamines; D006892:Hydroxydopamines; D001627:Bethanidine; D006145:Guanethidine