BTS 74 398 (1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-(3-diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in
MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmosets without provoking established
dyskinesia. However, it is not known whether
BTS 74 398 primes the basal ganglia for
dyskinesia induction. In this study, the ability of
BTS 74 398 to sensitize
6-hydroxydopamine (6-OHDA)-lesioned rats for the production of abnormal motor behaviours and the induction of striatal DeltaFosB were determined in comparison with
l-3,4-dihydroxyphenylalanine methyl
ester (
L-dopa). Acute administration of
BTS 74 398 induced a dose-dependent ipsilateral circling response in unilaterally 6-OHDA-lesioned rats whereas
L-dopa produced dose-dependent contraversive rotation. The ipsilateral circling response to
BTS 74 398 did not alter during 21 days of administration. In contrast,
L-dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both
L-dopa and
BTS 74 398 increased general motor activity and stereotypic behaviour. In
L-dopa-treated rats, orolingual, locomotive, forelimb and axial
abnormal movements developed whereas
BTS 74 398 produced only locomotion with a side bias but no other
abnormal movements. Sensitization of circling responses and the development of
abnormal movements in 6-OHDA-lesioned rats have been associated with the potential of
dopaminergic drugs to induce
dyskinesia. Furthermore, striatal DeltaFosB immunoreactivity, shown to correlate with
dyskinesia induction, was increased by
L-dopa but was unaffected by repeated
BTS 74 398 administration. The lack of such changes following repeated
BTS 74 398 treatment suggests that it may be an effective antiparkinsonian
therapy that is unlikely to produce
involuntary movements.