Serotonergic modulation of striatal D2 dopamine receptor binding in humans measured with positron emission tomography

Abstract

The modulating effect of serotonergic drugs on the striatal dopamine neurotransmission has remained controversial, and there are no published data on serotonin-dopamine interaction obtained from living human brain. Citalopram is a selective serotonin reuptake inhibitor widely used in the treatment of depression (20-40 mg/day). We measured the effects of acute (20 mg, per os) and chronic (20 mg/day for 14 days) doses of citalopram and placebo intake on [11C]-raclopride binding to striatal D2-receptors in eight healthy volunteers by using positron emission tomography. Although the effect magnitude was not large, the results indicate that chronic citalopram intake slightly decreases the raclopride binding which may reflect increased dopamine release in the striatum. In addition, after 14 days there was a high correlation between the citalopam plasma levels and the decrease in the [11C]-raclopride binding in both the caudate and the putamen, although statistically significant effect in the raclopride binding potential was more pronounced in the putamen. This report suggests functional interaction of brain dopaminergic and serotonergic systems in vivo in man.

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

“…Given its lack of D 2 -dopamine receptor affinity and its strong agonist activity at 5-HT 2 and 5-HT 1 receptors, the present result strongly suggest that psilocybin may increase dopamine release through 5-HT receptor activation. This mechanism is consistent with recent studies demonstrating increased striatal dopamine levels after acute administration of the 5-HT releaser and uptake inhibitor fenfluramine (Smith et al 1997) and chronic administration of the 5-HT uptake inhibitor citalopram (Tiihonen et al 1996) in normal subjects as assessed by PET and [ 11 C]raclopride. In animal studies, local application of 5-HT or 5-HT agonists by means of microdialysis was also reported to increase extracellular DA in the striatum (Benloucif and Galloway 1991;Benloucif et al 1993;Bonhomme et al 1995) and nucleus accumbens (Guan and McBride 1989;Parson and Justice 1993;Boulenguez et al 1996).…”

Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects

“…Consistent with the present results, a recent study that measured the effect of fenfluramine on [ 11 C]raclopride binding in the anesthetized baboon demonstrated a 33% reduction in specific binding (Mathis et al, unpublished data). Furthermore, a recently published study (47) demonstrated that acute administration of citalopram decreased [ 11 C]raclopride binding in human subjects, consistent with the fenfluramine results; however, the effect was much smaller (8% decrease) than the fenfluramine effect (consistent with the greater release of serotonin produced by fenfluramine compared with citalopram shown by in vivo microdialysis), and neuroendocrine levels were not measured.…”

Association between low‐activity serotonin transporter genotype and heroin dependence: Behavioral and personality correlates

“…On the other side, the significant difference evidenced in aggressiveness scores at BDHI between addicted individuals and healthy controls, independently from 5-HTT genotype subgroups, indicates that multiple psycho-biological factors, and not serotonin dysfunction alone, may probably affect impulsiveaggressive behavior in substance use disorders. In fact, changes in dopamine transporter density [Tiihonen et al, 1995[Tiihonen et al, , 1996 and dopamine receptors sensitivity [Blum et al, 1995] have been reported in substance use disorders, with the hypothesis of a complex behavioral syndrome, due to the coexistence of multiple genetic and environmental variables [Blum et al, 2000], that may be able to influence aggressive behavior.…”