Effects of the nicotinic acetylcholine receptor agonist SIB-1508Y on object retrieval performance in MPTP-treated monkeys: comparison with levodopa treatment.

This study assessed the relative potencies of levodopa/benserazide and the nicotinic acetylcholine receptor agonist SIB-1508Y on reversal of cognitive and motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys performing an object retrieval task. Monkeys previously taught to perform this task developed significant cognitive deficits after chronic low-dose MPTP exposure. These monkeys then received additional MPTP treatment to superimpose a parkinsonian movement disorder on their preexisting cognitive deficits. Levodopa/benserazide treatment significantly improved motor aspects of object retrieval performance but did not significantly improve cognition. SIB-1508Y (1 mg/kg) alone did not result in a statistically significant improvement in cognition or motor function in symptomatic MPTP-lesioned animals with deficits in both of these areas. However, the combination of SIB-1508Y and levodopa/benserazide caused significant improvements in both cognition and motor aspects of task performance, and did so at one third to one sixth of the levodopa dose necessary to improve only motor function. These results suggest the potential usefulness of SIB-1508Y and levodopa as adjunctive therapies to improve at least some of the cognitive and motor deficits associated with Parkinson's disease.