title: In vivo dopamine (DA) receptor binding and behavioural effects of the putative DA autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 in rats with a unilateral nigral 6-OH-DA lesion.
abstract: The in vivo dopamine (DA) receptor binding and behavioural properties of the recently characterised putative preferential DA autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 were studied in rats with a unilateral 6-OH-DA lesion of the substantia nigra. The main findings were a) that (+)-UH 232 and (+)-AJ 76 per se failed to produce significant turning behaviour, b) that both agents antagonised contralateral rotation caused by the DA agonist apomorphine, including a change of the characteristic two-peak apomorphine rotation pattern into a single peak, indicating that the DA antagonist properties of (+)-UH 232 and (+)-AJ 76 are retained also at denervation-sensitised postsynaptic DA receptors and--in support of this notion--c) that (+)-UH 232 and (+)-AJ 76 were able to displace the specific in vivo binding of the DA receptor agonist DP-5,6-ADTN in the denervated as well as in the intact striata of the 6-OH-DA-lesioned animals. Interestingly, in this regard (+)-UH 232 was significantly less efficient on the lesioned as compared to the intact side. The DP-5,6-ADTN-displacing effect of (+)-AJ 76 did not, however, differ between the intact and the denervated striatum. The implications of the present findings are discussed with particular reference to DA receptor sensitivity and adaptational phenomena.
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D007839:Functional Laterality / Q000502:physiology; D006892:Hydroxydopamines; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D006892:Hydroxydopamines; D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D015102:3,4-Dihydroxyphenylacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C051171:5-methoxy-1-methyl-2-(n-propylamino)tetralin; D016627:Oxidopamine; C045971:UH 232; D001058:Apomorphine