Age-dependent effects of 6-hydroxydopamine on locomotor activity in the rat

This experiment examined the effects on locomotor activity of intraventricular 6-hydroxydopamine (6-OHDA) administered to developing and adult rats. 6-OHDA was administered subsequent to pargyline treatment at 3 and 6 days of age; or 6-OHDA was administered subsequent to desmethylimipramine (DMI) treatment (6-OHDA/DMI) at 3 and 6 days of age, 11 and 14 days of age, 20 and 23 days of age, or 46 and 48 days of age. Locomotor activity of vehicle-treated rats assessed in stabilimeter cages peaked between 14 and 16 days of age and subsequently declined to levels characteristic of the adult. Treatment with pargyline and 6-OHDA at 3 days of age, or 6-OHDA/DMI at 3 and 6 or 11 and 14 days of age, did not alter the early rise in locomotor activity but prevented the decline in activity normally seen during the third and fourth weeks of life. When tested as adults, locomotor activity was greater in rats that had been treated with 6-OHDA/DMI at 3 and 6 and at 11 and 14 days of age than in those that had been treated at 20 and 23 days of age. Treatment with 6-OHDA/DMI at 46 and 48 days of age was without significant effect on locomotor activity. 6-OHDA (with pargyline pretreatment) produced large decreases in NE content in telencephalon and diencephalon and in dopamine (DA) content in striatum. 6-OHDA-DMI also produced large decreases in DA content in striatum and, in some of the treatment groups, only small decreases in norepinephrine (NE) content in telencephalon, diencephalon, and brain stem. These data suggest that the maturation of neuronal systems utilizing dopamine as a neurotransmitter is essential for the suppression of locomotor activity normally seen during development. The data further suggest that dopamine depletion per se does not lead to increased locomotor activity, but rather it is the destruction of dopamine-containing fibers prior to the normal period of locomotor suppression that increases locomotor activity.