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. Short communication.
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 = kon.Bmax). In vivo saturation experiments showed that Bmax for 3H-NMSP binding was relatively unchanged and an increase in the apparent association rate constant (kon) 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.
Inoue
O
O
Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Japan.
Wakahara
S
S
Kobayashi
K
K
Gee
A
A
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D013134:Spiperone; D016291:Dizocilpine Maleate; C039167:3-N-methylspiperone; D004298:Dopamine