Depletion and restoration of endogenous monoamines affects β-CIT binding to serotonin but not dopamine transporters in non-human primates

The radioligand [¹²³I]β-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 α-methyl-p-tyrosine (AMPT) to block dopamine production and measured [¹²³I]β-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]β-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]β-CIT binding to brainstem serotonin transporters but not to striatal dopamine transporters. Restoration of dopamine apparently did not affect [¹²³I]β-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]β-CIT displacement by endogenous dopamine was not observed. This study indicates that [ ¹²³I]β-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.