AN INCREASE IN THE INVIVO BINDING OF [H-3] SCH-23390 INDUCED BY MK-801 IN THE MOUSE STRIATUM

The effect of MK-801, a non-competitive NMDA antagonist, on the in vivo binding of [H-3]SCH 23390, a dopamine D1 receptor antagonist, was investigated in the mouse brain. The radioactivity following injection of the tracer was measured in the striatum, cerebral cortex and cerebellum. It was found that MK-801 increased the [H-3]SCH 23390 binding in the striatum in a dose-dependent manner, but did not influence the binding in the cerebral cortex. The kinetic analysis using the cerebellum as a reference region revealed that the apparent increase in [H-3]SCH 23390 binding in the striatum was mainly due to the increase in the input rate of the specific binding component. An in vivo saturation study using varying doses of [H-3]SCH 23390 indicated that the maximum binding sites available (B(max)) in the striatum was not altered by MK-801. As the rate constant K3 includes both B(max) and the association rate constant (k(on)), an increase in the rate constant k(on) in vivo was the primary factor in the changes in [H-3]SCH 23390 binding. The changes in the rate constant k(on) in vivo seem to be due to a NMDA receptor-mediated process. An in vivo binding method would be applicable for the investigation of the neural interaction between glutamatergic and dopaminergic neurons in intact brain.