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

Abstract

Neurologieal effects of neonatal depletion of dopamine (DA) were examined during adulthood using a eomprehensive battery of sensory and motor tests. On Postnatal Day 3, rat pups were pretreated with a noradrenaline uptake inhibitor followed by intraventricular mieroinfusion of the neurotoxin 6-hydroxydopamine (6-0HDA) to deplete permanently more than 95 % of striatal dopamine content in the medial and lateral caudate in most animals. Control animals reeeived the noradrenaline uptake inhibitor followed by intraventrieular infusions of vehicle only. It was confirmed that the sensory and motor behaviors ofthe neonatal dopamine-depleted (N-6-0HDA) animals were surprisingly intaet, eonsidering the well-established symptoms of comparable dopamine depletion in adult-operated animals; however, a detailed analysis revealed an array of ehronie abnormalities not previously deteeted. The severity of impairment was linked to the degree of dopamine deficieney. A group ofN-6-0HDA animals (during adulthood) were given an additional, but unilateral, infusion of 6-0HDA into the nigrostriatal tract to further deplete DA in one hemisphere. This treatment eaused severe behavioral asymmetries to emerge whieh were comparable to those observed following the same treatment in eontrol adults. The unusually small level of undepleted DA in the N-6-0HDA animals may have been suffieient 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 ofreeovery and sparing offunction, ofParkinson's disease, and of attention al disorders.Pennanent depletion of striatal dopamine (DA) can be achieved by intraventricular infusion of 6-hydroxydopamine (6-0HDA) into neonatal rats (Day 3) pretreated with a noradrenergic uptake inhibitor. The depletion can be nearly total, yet remarkably few behavioral deficits have been reported. Thus, adult-operated rats following intraventricular 6-0HDA infusion show aphagia, adipsia, akinesia, and orientation impainnents (Marshall, Richardson,

Preschool-Aged Children with Iron Deficiency Anemia Show Altered Affect and Behavior ,

“…Rats with neonatal dopamine depletion are hesitant to enter a novel environment or to engage in new tasks outside the familiar environment. Neonatal dopamine terminal damage leads to a life-long hyper-sensitivity to novel objects and experiences in an unfamiliar environment (49,50). Thus, early alterations in dopamine and associated pathways seem to have long-term effects on context-dependent attentional and affective responses.…”

Rescuing neurons from trans-synaptic degeneration after brain damage: Helpful, harmful, or neutral in recovery of function?

“…Perhaps projection sites receiving predominately inhibitory input are more susceptible because the neurons become dangerously hyperactive (Saji & Reis, 1987). Degeneration of target neurons may be more likely in infant-operated animals, which could help to explain certain instances of sparing of function after early lesions (Eidelberg, Nguyen, Polich, & Walder, 1989; Schallert et al, 1989).…”

“…Such release phenomena are frequently treated with blocking agents or surgical removal of the so-called disinhibited tissue, for example, neurosurgery or anticholinergic drugs in Parkinson's disease (Narabayashi, 1988, 1989; Schaltenbrand & Walker, 1982; Schallert, Whishaw, Ramirez, & Teitelbaum, 1978; Welch & Penfield, 1950). Thus, it is plausible that trans-synaptic degeneration could act as a natural process of control over the negative activity of disinhibited cells (Hernandez, Kiefel, et al, 1989; Lindner & Schallert, 1988; Schallert, Petrie, & Whishaw, 1989). In any case, without behavioural experiments, it would be premature to speculate about the significance of the above-described neuronal rescue procedure for clinical neurology, particularly since brain damage in people is seldom limited to the intrinsic cells of the striatum…”

Behavioral and Cytological Differences between Two Parkinson’s Disease Experimental Models

“…Parkinsonian-like tremors have been scarce in unilaterally 6-OHDA-lesioned rats [44,45]; nevertheless, Schallert et al [46] have reported infrequent tremors in the paw and the wrist of rats with almost complete dopamine denervation (either bilateral or unilateral). This tremor is observed when the paw is placed off the floor in a non-weight-bearing posture [46]. It is also known that bilaterally 6-OHDA-lesioned rats show most of the PD motor symptoms.…”