gms | German Medical Science

Objective: In Parkinson's disease (PD), the progressive loss of dopamine (DA) neurons in the substantia nigra leads to disturbed motor function, but cognitive disturbances, including attentional deficits and impulsivity, are increasingly recognized as disabling factors. Rats with 6-hydroxydopamine (6-OHDA) induced nigrostriatal lesions of DA neurons show significant motor impairment reminiscent of PD, and recent studies also indicate cognitive impairment in this model. We here investigated the effect of bilateral 6-OHDA lesions in rats on impulsivity and attention in an auditory oddball paradigm.

Methods: Rats were trained in a 3-class auditory oddball paradigm, where they had to nose poke a hole after an infrequent correct tone, which was rewarded by a pellet, but to ignore a frequent standard tone and infrequent distractor tone. After reaching a criterion of 90% correct hits, retrograde degeneration of DA neurons in the substantia nigra were induced by bilateral striatal injection of 6-OHDA (10 µg in 1µl PBS; n=12), sham-lesioned rats (controls; n=8) received vehicle. Four weeks after surgery the rats were re-tested in the oddball paradigm.

Results: After 6-OHDA lesions, rats show deteriorated attention, as indicated by a significant decrease in the hit rate to the correct tone. Additionally, the number of impulsive nose pokes was reduced compared to controls, which would indicate less impulsive behavior.

Conclusion: We conclude that rats with bilateral 6-OHDA lesions may be used to investigate the biological basis of attentional deficits in PD, and to develop and test new therapeutic strategies for these symptoms ranging from pharmacological treatment to neurosurgical intervention.