Postsynaptic striatal dopamine agonist or antagonist actions of (+) or (-) 3-PPP and modification after receptor...

The effects of the (+) and (-) enantiomers of 3-PPP on striatal postsynaptic dopaminergic (DAergic) receptors were studied using two rotation behaviour models in the rat. After unilateral deafferentation of the striatum by injection of 6-hydroxydopamine into the nigrostriatal DAergic tract and the development of hypersensitivity, apomorphine (0.025 mg/kg s.c.) and each of the enantiomers of 3-PPP (0.5-10 mg/kg s.c.) caused marked postural asymmetry and contralateral rotations by preferential stimulation of the DAergic receptors of the lesioned side. These rotations were antagonised by haloperidol (0.5 mg/kg i.p.). After unilateral inactivation of the nigrostriatal loop by extensive electrolytic lesion of the substantia nigra, apomorphine (0.5 mg/kg s.c.) and (+)3-PPP (25 and 50 mg/kg s.c.) caused ipsilateral rotations by stimulation of the striatal DAergic receptors on the intact side. By contrast (-)3-PPP (2-50 mg/kg i.p.) did not cause rotations and furthermore partially or completely opposed the action of apomorphine. These studies showed that (-)3-PPP has either an antagonistic or an agonistic action on the postsynaptic DAergic receptors or the striatum, respectively afferentiated or deafferentiated. Like apomorphine (+)3-PPP has a DAergic agonistic action under both circumstances.