Postsynaptic striatal dopamine agonist or antagonist actions of (+) or (-) 3-PPP and modification after receptor deafferentation.
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.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003714:Denervation; D018492:Dopamine Antagonists; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology; D016627:Oxidopamine; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013237:Stereoisomerism; D013569:Synapses
D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D010880:Piperidines; D011954:Receptors, Dopamine; D016627:Oxidopamine; C026539:preclamol; D001058:Apomorphine