Despite evidence linking
dopamine D(3) receptors to the etiology of
Parkinson's disease and
L-DOPA-induced
dyskinesia, the potential therapeutic utility of D(3) receptor
ligands remains unclear. In the present study, we investigated whether the selective D(3) receptor antagonist,
S33084, affects development and expression of abnormal
involuntary movements (AIMs), a behavioural correlate of
dyskinesia, in rats hemi-lesioned with
6-hydroxydopamine and chronically treated with
L-DOPA. The ability of
S33084, alone or in combination with
L-DOPA, to attenuate
6-hydroxydopamine induced motor deficits was also investigated employing a battery of behavioural tests. Acute administration of
S33084 (0.64 mg/kg, s.c.) did not attenuate the induction of AIMs in dyskinetic rats upon challenge with
L-DOPA (6 mg/kg, s.c.). Moreover,
S33084 (0.64 mg/kg) did not prevent the development of AIMs affecting axial, limb and orolingual muscles when chronically administered together with
L-DOPA (6 mg/kg for 21 days). However, both acute and chronic administration of
S33084 enhanced
L-DOPA-induced contralateral turning, suggesting potential antiparkinsonian properties. Furthermore,
S33084 (0.01-0.64 mg/kg) dose-dependently attenuated parkinsonian disabilities, including
bradykinesia, in drag and rotarod tests, although, in these procedures, the combination of
S33084 with
L-DOPA did not produce synergistic effect. It is concluded that sustained D(3) receptor blockade does not blunt
L-DOPA-induced
dyskinesia in hemiparkinsonian rats. However, D(3) receptor antagonism may be associated with antiparkinsonian properties. The clinical relevance of these observations will be of interest to explore further.