Enhancement of H-3-N-methylspiperone binding but not H-3-raclopride binding in mouse striatum by MK-801: evidence that factors other than competitionby endogenous dopamine are responsible for changes in D-2 receptor bindingin vivo

The effect of acute pretreatment with MK-801. on the binding in vivo of bot h H-3-N-methylspiperone (NMSP) and H-3-raclopride (RAC) were compared in mi ce. In the striatum, MK-801 significantly increase H-3-NMSP binding, wherea s no significant alterations in H-3-RAC binding were seen. In contrast, bin ding 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 in duced 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 bi nding 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 c ompetitive inhibition than is H-3-NMSP binding, these results strongly sugg est that factors other than competition by endogenous dopamine may contribu te to changes in receptor binding in vivo caused by NMDA-antagonism.