Interactions of 7-[3-(4-[2,3-Dimethylphenyl]piperazinyl)-propoxy]-2(lH)-quinolinone (OPC-4392) with 3H-Spiperone and 3H-SCH 23390 Binding in Rat Striatum: Effects of Lesions

7-[3-(4-[2,3-Dimethylphenyl]piperazinyl)propoxy]-2(lH)-quinolinone (OPC-4392), a presynaptic dopamine autoreceptor agonist and postsynaptic D-2 receptor antagonist (Yasuda et al, Life Sci.42:1941–1954,1988), was studied for its binding characteristics at 3H-SCH 23390-labeled dopamine D-l receptors and 3H-spiperone-labeled dopamine D-2 receptors in rat striatum. The binding affinity of OPC-4392 for 3H-spiperone-labeled D-2 receptors was 500 times higher than for 3H-SCH 23390-labeled D-l receptors. 6-Hydroxydopamine lesions of striatum and high-frequency current lesions of medial forebrain bundle did not affect the competition of OPC-4392 for 3H-spiperone binding. Kainic acid lesions of striatum significantly changed the one-site model fit to a two-site model fit of the competition curve of OPC-4392 for 3H-spiperone binding, suggesting that OPC-4392 competed with 3H-spiperone binding differently for postsynaptic dopamine D-2 receptors and for presynaptic dopamine autoreceptors.