Intraventricular 6-hydroxydopamine in the newborn rat and locomotor responses to drugs in infancy: no support for the dopamine depletion model of minimal brain dysfunction.

Abstract

Bilateral intraventricular injections of 6-hydroxydopamine (6-OHDA) after desmethylimipramine (DMI) in rats 1 and 2 days of age, severely depleted brain dopamine (DA) particularly in the neostriatum, where levels in adulthood were about 7% of control. Compared to vehicle-injected controls these rats were hyperactive only at 15 and 20 days of age, and in adulthood were impaired in a two-way avoidance. Rats with similar 6-OHDA treatment but without DMI pretreatment showed severe depletion of brain norepinephrine (NE) as well as DA, and were behaviorally similar to the DA-depleted only rats. This behavioral syndrome is similar to that reported after intracisternal injection of 6-OHDA in 5-day-old rats, which has been argued as a model for minimal brain dysfunction (MBD). Contrary to expectation from this model, however, challenge doses of either d-amphetamine or methylphenidate did not reduce, but instead increased activity of these rats. The 6-OHDA treatments also did not alter the enhancement of locomotor activity by scopolamine, which was present at 30 days but not at 15 days.