Neonatal dopamine depletion: Spared and unspared sensorimotor and attentional disorders and effects of further depletion in adulthood

Abstract

Neurological effects of neonatal depletion of dopamine (DA) were examined during adulthood using a comprehensive battery of sensory and motor tests. On Postnatal Day 3, rat pups were pretreated with a noradrenaline uptake inhibitor followed by intraventricular microinfusion of the neurotoxin 6-hydroxydopamine (6-OHDA) to deplete permanently more than 95% of striatal dopamine content in the medial and lateral caudate in most animals. Control animals received the noradrenaline uptake inhibitor followed by intraventricular infusions of vehicle only. It was confirmed that the sensory and motor behaviors of the neonatal dopamine-depleted (N-6-OHDA) animals were surprisingly intact, considering the well-established symptoms of comparable dopamine depletion in adult-operated animals; however, a detailed analysis revealed an array of chronic abnormalities not previously detected. The severity of impairment was linked to the degree of dopamine deficiency. A group of N-6-OHDA animals (during adulthood) were given an additional, but unilateral, infusion of 6-OHDA into the nigrostriatal tract to further deplete DA in one hemisphere. This treatment caused severe behavioral asymmetries to emerge which were comparable to those observed following the same treatment in control adults. The unusually small level of undepleted DA in the N-6-OHDA animals may have been sufficient to permit sparing of certain functions. Nevertheless, in most behavioral tests, the rats that were most extremely depleted by the neonatal surgery were highly resistant to the additional DA depletion. Thus, neonatal damage may impart unique neural changes in both DAergic and non-DAergic systems that are associated with spared functions. The data may have implications for developmental investigations of recovery and sparing of function, of Parkinson’s disease, and of attentional disorders.