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-1,1-dihydroquinoline treatment reduced specific [H-3]SCH 23390 (7-chloro-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% of saline-treated controls), entopeduncular nucleus (20%) and substantia nigra pars reticulata (23%). Similarly, specific [H-3]spiperone binding to D-2 DA receptors was decreased in the striatum (28-37% of saline-treated controls). However, [H-3]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 [H-3]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 [H-3]spiperone binding. In contrast, pretreatment with the D-1 DA agonist SKF 23390 (7,8-dihydroxy-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 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.