Mechanisms of selective depletion of brain regional noradrenaline by systemic 6-hydroxydopamine in newborn rats

Abstract

6-Hydroxydopamine injected systemically into newborn rats caused permanent depletions of the noradrenaline content of only certain brain regions. When 6-hydroxydopamine was given i.p. on days 1 and 2 after birth only the cortex, hippocampus and spinal cord were permanently depleted. 6-Hydroxydopamine given on days 9 and 10 after birth caused a permenent depletion predominantly from the cerebellum. Other regions were unaffected or were depleted for 4 days or less. The hypothalamus showed a gradual recovery of noradrenaline levels over a period of more than 20 days after injection, suggesting that only in this region was the apparent lack of effect of 6-hydroxydopamine due to neuronal regrowth. 6-Hydroxydopamine appeared to gain access to all regions except the pons-medulla when injected up to 10 days after birth, since at least temporary effects on noradrenaline storage were observed. 3H-Noradrenaline after i.p. injection was found in similar relative amounts in all brain regions in rats up to 20 days old. Thus regional differences due to age in the ability of 6-hydroxydopamine to reach various brain regions apparently do not explain the selective susceptibility to permenent depletion. It is suggested that the selective depletion must be due to interactions between the maturity of the adrenergic neurones and other factors such as their ability to take up or retain the 6-hydroxydopamine.