An autoradiographic study of the differential effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on striatal and extrastriatal D-1 and D-2 dopamine receptors in the rat.
The effect of in vivo administration of the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on striatal and extrastriatal D-1 and D-2 dopamine (DA) receptors was investigated in the rat. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline treatment reduced specific [3H]SCH 23390 (7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzaze pin e) binding to D-1 DA receptors in the striatum (42-46% of saline-treated controls), entopeduncular nucleus (20%) and substantia nigra pars reticulata (23%). Similarly, specific [3H]spiperone binding to D-2 DA receptors was decreased in the striatum (28-37% of saline-treated controls). However, [3H]spiperone binding in the substantia nigra pars compacta (67%) was much less affected. In vivo pretreatment with the D-1 DA antagonist SCH 23390 selectively and dose dependently protected [3H]SCH 23390 binding against the effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in the striatal/extrastriatal regions. Pretreatment with the D-2 DA antagonist raclopride or the D-2 DA agonist quinpirole selectively protected [3H]spiperone binding. In contrast, pretreatment with the D-1 DA agonist SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) not only protected [3H]-SCH 23390 binding but at very high doses protected striatal [3H]spiperone binding. The differential alkylating effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline on striatal vs extrastriatal D-1 and D-2 DA receptors may be related to their post- (striatal DA receptors) and pre-synaptic (extrastriatal DA receptors) localizations, respectively. The present results further demonstrate that in vivo, SCH 23390 and raclopride/quinpirole retain their D-1 and D-2 DA receptor selectivity.
Gnanalingham
K K
KK
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, U.K.
Hunter
A J
AJ
Jenner
P
P
Marsden
C D
CD
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology; D003720:Densitometry; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000493:pharmacokinetics
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004873:Ergolines; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D013134:Spiperone; C000470:EEDQ; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine