Depletion and restoration of endogenous monoamines affects beta-CIT binding to serotonin but not dopamine transporters in non-human primates.
The radioligand [123I]beta-CIT binds to dopamine transporters in striatum and to serotonin transporters in brainstem. Endogenous dopamine or serotonin may compete with radioligand binding at monoamine transporters. We used alpha-methyl-p-tyrosine (AMPT) to block dopamine production and measured [123I]beta-CIT binding before and after endogenous dopamine was restored by IV administration of the dopamine precursor L-dihydroxyphenylalanine (L-DOPA) in rhesus monkeys. P-chlorophenylalanine (pCPA) was used to inhibit serotonin production, and [123I]beta-CIT binding was assessed before and after IV administration of the serotonin precursor 5-hydroxy-L-tryptophan (L-5-HTP) restored endogenous serotonin. Pretreatment with benserazide blocked peripheral decarboxylization in both paradigms. Serotonin restoration measurably displaced [123I]beta-CIT binding to brainstem serotonin transporters but not to striatal dopamine transporters. Restoration of dopamine apparently did not affect [123I] beta-CIT binding to striatal dopamine transporters. However, dopamine restoration reduced radioligand binding to brainstem serotonin transporters, most likely due to dopamine release from serotonin neurons following L-DOPA administration. The higher striatal density of dopamine transporters relative to dopamine concentrations may explain why [123I] beta-CIT displacement by endogenous dopamine was not observed. This study indicates that [123I]beta-CIT binding in brainstem (raphe area) is affected by endogenous serotonin release in vivo and that L-DOPA treatment may cause serotonin neurons in the brainstem to corelease dopamine.
Heinz
A
A
Department of Psychiatry, Charité University Medicine Berlin, Campus Charité Mitte, Berlin, Germany. andreas.heinz@charite.de
Jones
D W
DW
Zajicek
K
K
Gorey
J G
JG
Juckel
G
G
Higley
J D
JD
Weinberger
D R
DR
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D015306:Biogenic Monoamines; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D019805:alpha-Methyltyrosine; D006916:5-Hydroxytryptophan; D003042:Cocaine