Neonatal 6-hydroxydopamine potentiates clonidine's locomotor effects throughout maturation in the rat.
Newborn rats were administered 6-hydroxydopamine (6-OHDA) systemically (2 X 100 micrograms/g) or vehicle and subsequently tested for their locomotor response to one of three doses of clonidine (10, 100 or 1000 micrograms/kg) at either 10, 20, 30 or 50 days of age. Clonidine caused a dose-related increase in activity in 10-day-old rats and this effect was potentiated in the 6-OHDA-treated rats. At 20 days, clonidine did not affect activity in the vehicle rats but at the highest dose, increased that of the 6-OHDA rats. At 30 days, clonidine again did not affect activity in the vehicle rats but the 1000 micrograms/kg (when compared to the 100 micrograms/kg) dose, significantly increased activity of the 6-OHDA rats. A biphasic effect of clonidine was apparent at 50 days. At this age the 6-OHDA treatment exaggerated the depressant effect of the 100 micrograms/kg dose. Thus, neonatal-OHDA generally potentiated the locomotor response to clonidine despite the fact that the effect of the drug changed with age. It is concluded that the locomotor effects of clonidine are mediated through alpha 2 adrenoceptors which are not located on noradrenergic terminals but rather are postsynaptic to them. With maturation, the "functional wiring" of these terminals appears to be altered.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002395:Catecholamines / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013563:Sympathectomy, Chemical
D002395:Catecholamines; D006892:Hydroxydopamines; D016627:Oxidopamine; D003000:Clonidine