Similarities and Differences Between High-Affinity Binding Sites for Cocaine and Imipramine in Mouse Cerebral Cortex

Previously we found close similarities between high-affinity binding sites for 3H]cocaine and those for 3H]imipramine in the mouse cerebral cortex in regard to their association with neuronal uptake of serotonin. In the present study we investigated whether the two ligands bind to the same site. The two ligands had the following high-affinity binding properties in common: localization in both synaptosomal and microsomal fractions; vulnerability to treatment with N-ethylmaleimide, trypsin, and phospholipase A2; and resistance to exposure to dithiothreitol. In contrast, cocaine binding in the cerebral cortex was more sensitive to heat inactivation than imipramine binding. In addition, the mechanism by which cocaine inhibited 3H]imipramine binding differed from that by which imipramine inhibited 3H]cocaine binding. These data suggest that the high-affinity binding sites for 3H]cocaine and 3H]imipramine in the cerebral cortex are distinct entities.