Motor effects of (−)-OSU6162 in primates with unilateral 6-hydroxydopamine lesions

Abstract

The effects of the novel compound, (−)-OSU6162 (( S)-(−)-3-methylsulfonylphenyl-1-propylpiperidine), on rotational behavior induced by dopamine receptor agonists was investigated in common marmosets ( Callithrix jacchus) with unilateral 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 hydrochloridum), l-DOPA (3,4-dihydroxyphenylalanine), and the dopamine D2 receptor agonist, quinpirole ( trans-(−)-4 aR-4,4 a,5,6,7,8,8 a,9-octahydro-5-propyl-1 H-pyrazolol[3,4- g]quinoline hydrochloride), without inducing motor impairment such as akinesia or dystonia. In addition, treatment with (−)-OSU6162 for 5 consecutive days almost completely abolished the rotational behavior provoked by apomorphine and produced a transient subsensitization of such apomorphine-induced effects after it was discontinued. Moreover, pretreatment with (−)-OSU6162 in two monkeys augmented the rotational behavior elicited by the dopamine D1 receptor agonists, SKF-81297 ( R(+)-6-chloro-7,8,dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrobromide) and A-77636 ((−)-(1 R,3 S)-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1 H-2-benzopyran hydrochloride). The findings indicate that (−)-OSU6162 can exert indirect state-dependent effects that differentially affect dopamine D1 and dopamine D2 receptor agonist-induced behavior.