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-ethoxyc arbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on striatal and extrastri atal D-1 and D-2 dopamine (DA) receptors was investigated in the rat. N-ethoxycarbonyl-2-ethoxy-1,1-dihydroquinoline treatment reduced speci fic [H-3]SCH 23390 -8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1- H-3-benzazepine) binding to D-1 DA receptors in the striatum (42-46% o f saline-treated controls), entopeduncular nucleus (20%) and substanti a nigra pars reticulata (23%). Similarly, specific [H-3]spiperone bind ing to D-2 DA receptors was decreased in the striatum (28-37% of salin e-treated controls). However, [H-3]spiperone binding in the substantia nigra pars compacta (67%) was much less affected. In vivo pretreatmen t with the D-1 DA antagonist SCH 23390 selectively and dose dependentl y protected [H-3]SCH 23390 binding against the effects of N-ethoxycarb onyl-2-ethoxy-1,2-dihydroquinoline in the striatal/extrastriatal regio ns. Pretreatment with the D-2 DA antagonist raclopride or the D-2 DA a gonist quinpirole selectively protected [H-3]spiperone binding. In con trast, pretreatment with the D-1 DA agonist SKF 23390 roxy-1-phenyl-2, 3,4,5-tetrahydro-1H-3-benzazepine) not only protected [H-3]-SCH 23390 binding but at very high doses protected striatal [H-3]spiperone bindi ng. The differential alkylating effects of N-ethoxycarbonyl-2-ethoxy- 1,2-dihydroquinoline on striatal vs extrastriatal D-1 and D-2 DA recep tors may be related to their post- (striatal DA receptors) and pre-syn aptic (extrastriatal DA receptors) localizations, respectively. The pr esent results further demonstrate that in vivo, SCH 23390 and raclopri de/quinpirole retain their D-1 and D-2 DA receptor selectivity.