Motor effects of (-)-OSU6162 in primates with unilateral 6-hydroxydopaminelesions

The effects of the novel compound, (-)-OSU6162 ((S)-(-)-3-methylsulfonylphe nyl-1-propylpiperidine), on rotational behavior induced by dopamine recepto r agonists was investigated in common marmosets (Callithrix jacchus) with u nilateral 6-hydroxydopamine lesions. (-)-OSU6162 per se displayed no effect on the animals' behavior. On the other hand, pretreatment with (-)-OSU6162 attenuated rotational behavior induced by apomorphine (apomorphini hydroch loridum), L-DOPA (3,4-dihydroxyphenylalanine), and the dopamine D2 receptor agonist, quinpirole (trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H -pyrazolol[3,4-g]quinoline hydrochloride), without inducing motor impairmen t such as akinesia or dystonia. In addition, treatment with (-)-OSU6162 for 5 consecutive days almost completely abolished the rotational behavior pro voked by apomorphine and produced a transient subsensitization of such apom orphine-induced effects after it was discontinued. Moreover, pretreatment w ith (-)-OSU6162 in two monkeys augmented the rotational behavior elicited b y the dopamine D1 receptor agonists, SKF-81297 (R(+)-6-chloro-7,8,dihydroxy -1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide) and A-77636 ((- )-(1R,3S)-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzop yran hydrochloride). The findings indicate that (-)-OSU6162 can exert indir ect state-dependent effects that differentially affect dopamine D1 and dopa mine D2 receptor agonist-induced behavior. (C) 2000 Elsevier Science B.V. A ll rights reserved.