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.
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.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D005260:Female; D006801:Humans; D006892:Hydroxydopamines / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats
D002395:Catecholamines; D006892:Hydroxydopamines; D004298:Dopamine