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A procedure was developed to study black versus white and horizontal versus vertical pattern visual discriminations in a swimming pool. The effects of central cholinergic muscarinic receptor blockade by atropine sulfate was then evaluated. The drug treatment impaired acquisition but not retention. Behavioral observations showed that the control rats used a number of strategies during the process of problem solving that facilitated acquisition of the discrimination. Through modifications of training procedures, the processes of strategy selection and discrimination learning were dissociated. Cholinergic blockade was found to impair strategy selection but not discrimination learning. The results question the widely held view that cholinergic systems are involved in learning and memory and suggest instead that cholinergic systems are involved in the selection of the movements or strategies that are prerequisite for learning.

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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,

Swiss Webster (SW), Dilute Brown Agouti (DBA), and Deer Mice (DM) were tested for acquisition and retention of a learning set place task in the Morris water maze. The learning set consisted of daily placing the hidden platform sequentially at 1 of 4 separate locations in the pool. All animals swam for 63 days in this version of the water task. SW animals were unable to find the platform reliably. The time taken by DBA and DM animals in escaping the pool declined rapidly, reaching asymptote within 21 days. The DM animals reached the platform significantly faster than either SW or DBA mice. Analyses of swim path selection used by the 3 strains indicated clearly that DM mice were the most systematic in the selecting and sequencing from a variety of potential strategies the appropriate methods necessary for the most efficient solution of the problem. The present results suggest that in light of the differences between strains observed in swimming behaviors, investigation of strain differences in the neuroanatomic structures believed to be related to the solving of spatial problems might be useful.