Enhancement of [¹²³I]β-CIT binding in the striatum with clomipramine: Is there a serotonin-dopamine interaction?

Many reports support the concept of serotonergic-dopaminergic interaction in the brain. However, at present, there are few methods to study this relationship in vivo. The purpose of this study was to investigate the effect of serotonin (5-HT) uptake inhibitor, clomipramine, on a dopamine (DA) transporter ligand, [¹²³I]β-CIT (RTI-55), in rat brain. Dose-dependent changes in [¹²³I]β-CIT specific binding induced by clomipramine were studied in the striatum (rich in DA transporter) and the hypothalamus (rich in 5-HT transporter). The changes in the time-activity curves of [¹²³I]β-CIT specific binding after clomipramine injection were also examined in these two regions. Using the cerebellum as the reference region, κ₃ and κ₄ values with and without clomipramine administration were estimated by a two-compartment kinetic analysis. Clomipramine inhibited [¹²³I]β-CIT specific binding in the hypothalamus, but enhanced its specific binding in the striatum in a dose-dependent manner. Kinetic analysis showed that κ₃ in the striatum was increased by 55%. In conclusion, enhancement of [¹²³I]β-CIT binding in the striatum after clomipramine administration indicated the possibility of 5-HT-DA interaction.