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

The effect of acute pretreatment with MK-801. on the binding in vivo of both H-3-N-methylspiperone (NMSP) and H-3-raclopride (RAC) were compared in mice. In the striatum, MK-801 significantly increase H-3-NMSP binding, whereas no significant alterations in H-3-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 H-3-NMSP binding induced by MK-801 was due to an increase in the rate constant k(3) (k(3) = 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 k(3) for H-3-NMSP binding. As H-3-RAC binding is known to be much more sensitive to competitive inhibition than is H-3-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.