Selective serotonin reuptake inhibitor (SSRI) modulation of striatal dopamine measured with [¹¹C]‐raclopride and positron emission tomography

Abstract

The effect of a pharmacologic increase in serotonin concentrations on striatal dopamine (D2) receptor availability has been measured in several studies using positron emission tomography (PET) and the radiotracer [11C]-raclopride as a method for the in vivo imaging of serotonin modulation of striatal dopamine in human subjects. These studies have shown that an acute increase in serotonin concentrations produced a decrease in striatal D2 receptor availability. The current study was undertaken to measure the effects of a more pharmacologically selective serotonergic agent compared to previous studies, the serotonin reuptake inhibitor, citalopram, on striatal D2 receptor availability. Twelve healthy control subjects underwent two PET scans performed on the same day following i.v. administration of saline (Scan 1) and citalopram (Scan 2, 40 mg, i.v.). The [11C]-raclopride data were analyzed with a graphical analysis method using the cerebellum as the input function. Plasma levels of citalopram, cortisol, and prolactin were measured. The citalopram concentrations peaked at the end of infusion (EOI) and remained relatively consistent from 30 min to 3 h postinfusion. An increase in cortisol and prolactin concentrations was observed from the EOI until 60 min after the EOI. A significant decrease in striatal D2 receptor availability was observed after citalopram infusion (−5%), presumably due to an increase in endogenous dopamine concentrations. In summary, i.v. administration of the selective serotonin reuptake inhibitor, citalopram, produced modest reductions in striatal D2 receptor availability, consistent with other human [11C]-raclopride studies using less pharmacologically selective serotonergic agents.

Serotonin Modulation of Cerebral Glucose Metabolism in Depressed Older Adults

“…As has been reviewed previously, given that the regional pattern of metabolic alterations extends beyond the primary serotonergic projections, the metabolic alterations are likely to reflect secondary changes in other neurochemical systems known to be modulated by serotonin and located within the cortical and limbic regions affected (including glutamate, dopamine and acetylcholine 19, 54-56). For example, the same dose, route and time course of administration of citalopram has been shown to produce an increase in endogenous dopamine in healthy control subjects (as shown by an decrease in dopamine D2 receptor availability measured with PET and [11C]-raclopride) as the metabolic alterations reported in the present study (57). …”

Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases

“…Similar results were obtained upon infusion of serotonin into the hippocampus of AD mice [184]. In humans, lower cortical amyloid levels were observed in participants who had been administered SSRIs in the past five years [186]. These transporters remain at much lower levels in patients having AD.…”

Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients

“…For SPM analysis, all images were Gaussian-filtered with 8mm FWHM to minimize inter-image variability. Intensity normalization was subsequently performed with scaling of [ 18 F]-AV45 and FDG activities to the cerebellum defined by the Hammers Atlas [23]. Implicit masking was used to compare only those voxels with valid values in all subjects after PVEC.…”