Comparison of two radioiodinated ligands of dopamine D2 receptors in animal models: iodobenzamide and iodoethylspiperone.
Several iodinated compounds have been developed for in vivo exploration of dopamine D2 receptors by SPECT. It is of great value to understand if the same information could be obtained with different radioligands. For this purpose, we compared in vivo properties of two iodinated ligands, iodoethylspiperone (IES) and iodobenzamide (IBZM), using different pharmacological and lesioning treatments in rats. Cerebral biodistribution performed by ex vivo autoradiograms and dissection of brain areas showed that IES and IBZM bound specifically to D2 receptors since a pre-injection of haloperidol prevented accumulation of both ligands. In contrast, when haloperidol was injected after IES or IBZM, only IBZM was displaced from its binding sites. This could be explained partly by a process of dopamine-dependent internalization with IES. The response to striatal quinolinic acid infusion for lesioning post-synaptic neurons was very different for IES and IBZM. In this model a decrease in IBZM accumulation occurred, corresponding to the loss of D2 receptors located on post-synaptic neurons. In contrast, a unexpected increase in IES accumulation was observed on the lesioned side. From these results we concluded that IES and IBZM, two iodinated ligands belonging to different pharmacological families, bound specifically to dopamine D2 receptors. However they have different properties in animal models. Therefore, it appears that IBZM is a more suitable ligand than IES to detect modifications of D2 receptors by in vivo exploration.
Pellevoisin
C
C
INSERM U 316, Laboratoire de Biophysique médicale et pharmaceutique, Tours.
Chalon
S
S
Zouakia
A
A
Dognon
A M
AM
Frangin
Y
Y
Baulieu
J L
JL
Besnard
J C
JC
Guilloteau
D
D
D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism*; D008297:Male; D011859:Radiography; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism
D001549:Benzamides; D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2; C065265:iodoethylspiperone; D013134:Spiperone; C037689:benzamide; D004298:Dopamine