Enhancement of ³H-N-methylspiperone binding but not ³H-raclopride binding in mouse striatum by MK-801: evidence that factors other than competition by endogenous dopamine are responsible for changes in D₂ receptor binding in vivo

Summary.

The effect of acute pretreatment with MK-801 on the binding in vivo of both ³H-N-methylspiperone (NMSP) and ³H-raclopride (RAC) were compared in mice. In the striatum, MK-801 significantly increase ³H-NMSP binding, whereas no significant alterations in ³H-RAC binding were seen. In contrast, binding in the cerebral cortex of both radiolabeled ligands was not changed by MK-801. Kinetic analysis revealed that the increase in ³H-NMSP binding induced by MK-801 was due to an increase in the rate constant k₃ (k₃ = k_on·B_max). In vivo saturation experiments showed that B_max for 3H-NMSP binding was relatively unchanged and an increase in the apparent association rate constant (k_on) was the main reason for an increase in the k₃ for ³H-NMSP binding. As ³H-RAC binding is known to be much more sensitive to competitive inhibition than is ³H-NMSP binding, these results strongly suggest that factors other than competition by endogenous dopamine may contribute to changes in receptor binding in vivo caused by NMDA-antagonism.