In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram

Klein, Nikolas; Sacher, Julia; Geiss-Granadia, Thomas; Attarbaschi, T.; Mossaheb, Nilufar; Lanzenberger, Rupert; Pötzi, Christian; Holik, A.; Spindelegger, Christoph; Asenbaum, S.; Dudczak, Robert; Tauscher, Johannes; Kasper, Siegfried

doi:10.1007/s00213-006-0486-0

Cited by 74 publications

(65 citation statements)

References 42 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, interfering with serotonergic signaling of optogenetically targeted raphe neurons decreased behavior that required maintenance of motivation (Liu et al, 2014). Thus, another possible explanation for the main physiologic role of 5-HT may be to increase patiencebefore inhibiting or activating to avoid punishment or achieve a reward (Miyazaki et al, 2012a).…”

Section: Discussionmentioning

confidence: 99%

“…rs25531 (A Ͼ G) and rs25532 (C Ͼ T) have been identified and, when not controlled for, can lead to 5-HTT expression levels for the L allele similar to those seen for the S allele (Hu et al, 2006;. Therefore, to maximize hypothesized group differences in 5-HTT expression, we analyzed these two additional SNPs in all L/L allele carriers and excluded low expressing genotypes.…”

Section: Methodsmentioning

confidence: 99%

“…We used an acute blockade of 5-HTTs via the intravenous application of a selective serotonin reuptake inhibitor (SSRI) in a double-blind crossover design in human subjects. The genetic background was controlled for by an extreme group approach: from a large sample of genotyped Caucasian subjects (n ϭ 878), two groups based on estimated highest (LL; n ϭ 17) and lowest (SS; n ϭ 15) 5-HTT expression were selected (Hu et al, 2006). We hypothesized increased PES (Crockett et al, 2012) and not PCS in S allele carriers, because PES involves evaluation of subjectively aversive events (Boureau and Dayan, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Serotonin Reuptake Inhibitors and Serotonin Transporter Genotype Modulate Performance Monitoring Functions But Not Their Electrophysiological Correlates

et al. 2015

View full text Add to dashboard Cite

Serotonin (5-HT) has been hypothesized to be implicated in performance monitoring by promoting behavioral inhibition in the face of aversive events. However, it is unclear whether this is restricted to external (punishment) or includes internal (response errors) events. The aim of the current study was to test whether higher 5-HT levels instigate inhibition specifically in the face of errors, measured as post-error slowing (PES), and whether this is represented in electrophysiological correlates of error processing, namely error-related negativity (ERN) and positivity. Therefore, from a large sample of human subjects (n ϭ 878), two extreme groups were formed regarding hypothesized high and low 5-HT transporter (5-HTT) expression based on 5-HTTLPR and two additional single nucleotide polymorphisms (rs25531, rs25532). Seventeen higher (LL) and 15 lower (SS) expressing Caucasian subjects were administered the selective serotonin reuptake inhibitor (SSRI) citalopram (10 mg) intravenously in a double-blind crossover design. We found pharmacogenetic evidence for a role of 5-HT in mediating PES: SSRI administration increased PES in both genetic groups, and SS subjects displayed higher PES. These effects were absent on post-conflict slowing. However, ERN and error positivity were unaffected by pharmacogenetic factors, but ERN was decoupled from behavioral adaptation by SSRI administration in the LL group. Thus, pharmacogenetic evidence suggests that increased 5-HT levels lead to behavioral inhibition in the context of internal aversive events, but electrophysiological correlates of performance monitoring appear unrelated to the 5-HT system. Therefore, our findings are consistent with theories suggesting that 5-HT mediates the link between aversive processing and inhibition.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Serotonin Reuptake Inhibitors and Serotonin Transporter Genotype Modulate Performance Monitoring Functions But Not Their Electrophysiological Correlates

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Encouraging results from human studies using the leading PET imaging agent, [ 11 C]DASB (3) (Table 1) have demonstrated the potential of studying drug occupancy in living human brains [9][10][11][12][13][14]. Progress has also been made in imaging SERT binding sites in the brain by single photon emission computed tomography (SPECT) [15][16][17]. SPECT imaging studies using [ 123 I]ADAM (2) were performed to investigate SERT occupancies after a single dose of escitalopram or citalopram.…”

Section: Introductionmentioning

confidence: 99%

“…SPECT imaging studies using [ 123 I]ADAM (2) were performed to investigate SERT occupancies after a single dose of escitalopram or citalopram. A test-retest study showed that the drug occupancy in the brain could be correlated with the level of antidepressant dose with good reproducibility [13,15,16,[18][19][20].…”

Section: Introductionmentioning

confidence: 99%

5-Chloro-2-(2′-((dimethylamino)methyl)-4′-iodophenylthio)benzenamine: a new serotonin transporter ligand

Oya

Choi

Kung

et al. 2007

Nuclear Medicine and Biology

View full text Add to dashboard Cite

Two novel ligands with a 4′-substitution on the phenyl ring B of biphenylthiol: 5-chloro-2-(2′-((dimethylamino)methyl)-4′-iodophenylthio)benzenamine, 7, and 2-(2′-((dimethylamino) methyl)-4′-methoxyphenylthio)-5-iodobenzenamine, 8, were prepared and tested as potential serotonin transporter (SERT) imaging agents. The new ligands displayed extremely high binding affinities to SERT (K i = 0.22 ± 0.09 and 0.11 ± 0.04 nM, respectively), with very low binding affinities to dopamine and norepinephrine transporters (K i > 1, 000 nM). The corresponding [ 125 I]7 and [ 125 I] 8 were successfully prepared from the tri-n-butyltin derivatives. They showed good brain uptakes and prolonged retention after iv injection in rats (brain uptake was 1.77 and 0.98 %dose/g for [ 125 I] 7 and 0.92 and 0.29 %dose/g for [ 125 I]8 at 2 and 120 minutes, respectively). Significantly, [ 125 I]7 showed excellent uptake and prolonged retention in the hypothalamus, where the SERT concentration is the highest. The hypothalamus/cerebellum ratios (target to background ratios) were 4.24, 7.10, 8.24 and 12.6 at 2, 4, 6 and 12 hours, respectively. The hypothalamus/cerebellum ratios for [ 125 I]8 were 3.97, 5.57 and 5.06 at 1, 2 and 4 hours, respectively. Adding the 4′-iodo-group to the phenyl ring B of 7 appeared to reduce the rate of clearance from the brain, and the kinetics favored uptake and retention in the hypothalamus. The localization of [ 125 I]7 in the hypothalamus region in the brain of rats could be blocked by pretreatment with (+)McN5652, escitalopram and ADAM (2), all selective serotonin transporter ligands (at 2 mg/Kg dose, iv, 5 min pretreatment). Ex vivo autoradiograms of rat brain sections (at 4 hr after iv injection of [ 125 I]7) showed intense labeling in regions of the brain known to have high SERT density. The excellent selective uptake and retention in the hypothalamus region suggests that [ 123 I]7 is a potential lead compound for developing new imaging agents targeting SERT binding sites with single photon emission computed tomography (SPECT).

show abstract

One‐week escitalopram intake alters the excitation–inhibition balance in the healthy female brain

Zsido

Molloy

Cesnaite

et al. 2022

Human Brain Mapping

View full text Add to dashboard Cite

Neural health relies on cortical excitation-inhibition balance (EIB). Previous research suggests a link between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear.Thus, in a randomized double-blind study, we administered a clinically relevant dose of 20 mg escitalopram for 7 days (time when steady state is achieved) in 59 healthy women (28 escitalopram, 31 placebo) on oral contraceptives. We acquired restingstate electroencephalography data at baseline, after a single dose, and at steady state. We assessed 1/f slope of the power spectrum as a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Escitalopram-intake was associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after a single dose of escitalopram was associated with 1/f slope at steady state. Higher plasma escitalopram levels at a single dose were associated with better maintenance of these EIB changes throughout the drug administration week. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the lens through which we map the human brain by testing an interventional psychopharmacological design in a clearly defined endocrinological state.

show abstract

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram

Cited by 74 publications

References 42 publications

Serotonin Reuptake Inhibitors and Serotonin Transporter Genotype Modulate Performance Monitoring Functions But Not Their Electrophysiological Correlates

Serotonin Reuptake Inhibitors and Serotonin Transporter Genotype Modulate Performance Monitoring Functions But Not Their Electrophysiological Correlates

5-Chloro-2-(2′-((dimethylamino)methyl)-4′-iodophenylthio)benzenamine: a new serotonin transporter ligand

One‐week escitalopram intake alters the excitation–inhibition balance in the healthy female brain

Contact Info

Product

Resources

About