EFFECTS OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR AGONIST SIB-1508Y ON OBJECT RETRIEVAL PERFORMANCE IN MPTP-TREATED MONKEYS - COMPARISON WITHLEVODOPA 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-tetrahydrop yridine (MPTP)-treated monkeys performing an object retrieval task. Mo nkeys previously taught to perform this task developed significant cog nitive deficits after chronic low-dose MPTP exposure. These monkeys th en received additional MPTP treatment to superimpose a parkinsonian mo vement disorder on their preexisting cognitive deficits. Levodopa/bens erazide treatment significantly improved motor aspects of object retri eval performance but did not significantly improve cognition. SIB-1508 Y (1 mg/kg) alone did not result in a statistically significant improv ement in cognition or motor function in symptomatic MPTP-lesioned anim als 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 on e third to one sixth of the levodopa dose necessary to improve only mo tor function. These results suggest the potential usefulness of SIB-15 08Y and levodopa as adjunctive therapies to improve at least some of t he cognitive and motor deficits associated with Parkinson's disease.