5-Hydroxytryptamine 1a (5-HT 1a ) receptor agonists, such as sarizotan and tandospirone, are reported to reduce levodopainduced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's disease without worsening motor disability. However, these compounds are not specific for 5-HT 1a receptors and also possess dopamine antagonist actions. We now report on the effects of (2R), a selective 5-HT 1a agonist lacking dopaminergic activity, on motor disability and dyskinesia (chorea and dystonia) in levodopa-primed MPTP-treated common marmosets. Administration of (R)-(ϩ)-8-OHDPAT (0.2, 0.6, and 2.0 mg/kg s.c), in conjunction with levodopa/carbidopa (12.5 mg/kg each p.o.) to levodopa-primed animals, dose-dependently reduced levodopa-induced chorea but did not affect dystonic movements. However, (R)-(ϩ)-8-OHDPAT treatment also reduced locomotor activity and the reversal of motor disability. Administration of (R)-(ϩ)-8-OHDPAT alone had no effects of motor behaviors. The effects of (R)-(ϩ)-8-OHDPAT on levodopa-induced motor behaviors were antagonized by the 5-HT 1a recep-(1.0 mg/kg s.c.). Administration of (R)-(ϩ)-8-OHDPAT (0.6 mg/kg s.c.) also reduced chorea produced by the administration of the D 2 /D 3 dopamine receptor agonist pramipexole (0.06 mg/kg p.o.) to levodopa-primed MPTP-treated animals. However, again the increase in locomotor activity and reversal of motor disability produced by pramipexole were also inhibited. These data suggest that selective 5-HT 1a agonists do not provide an effective means of suppressing levodopa-induced dyskinesia, except with worsening of parkinsonism.
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