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

Fujita, Masahiro; Takatoku, Keizo; Matoba, Yoshinori; Nishiura, Masaru; Kobayashi, Kaoru; Ito, Osamu

doi:10.1007/s002590050069

Cited by 8 publications

(12 citation statements)

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“…125 I]b-CIT binding (Fujita et al, 1997). The increase was correlated with the blockade of midbrain SERT binding by the drug, suggesting an underlying interaction between serotonin and dopamine systems.…”

Section: Discussionmentioning

confidence: 77%

Changes in Human In vivo Serotonin and Dopamine Transporter Availabilities during Chronic Antidepressant Administration

Kugaya

Seneca

Snyder

et al. 2002

Neuropsychopharmacol

152

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Few studies have demonstrated in vivo alterations of human serotonin and dopamine transporters (SERTS and DATS) during antidepressant treatment. The current study measured these transporter availabilities with [123 I]b-CIT single photon emission computed tomography (SPECT) during administration of selective serotonin reuptake inhibitors (SSRIs) or a non-SSRI, bupropion. A total of 17 healthy human subjects were randomly assigned to two different treatment protocols: (1) citalopram (40 mg/day) followed by augmentation with bupropion (100 mg/day) or (2) bupropion (100-200 mg/day) for 16 days. Citalopram significantly inhibited [123 I]b-CIT binding to SERT in brainstem (51.4%) and diencephalon (39.4%) after 8 days of administration, which was similarly observed after 16 days. In contrast, citalopram significantly increased striatal DAT binding by 15-17% after 8 and 16 days of administration. Bupropion and its augmentation to citalopram did not have a significant effect on DAT or SERT. In 10 depressed patients who were treated with paroxetine (20 mg/day), a similar increase in DAT and inhibition of SERT were observed during 6 weeks treatment. The results demonstrated the inhibition of SERT by SSRI in human in vivo during the chronic treatment and, unexpectedly, an elevation of DAT. This apparent SSRI-induced modulation of the dopamine system may be associated with the side effects of these agents, including sexual dysfunction.

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Section: Discussionmentioning

confidence: 77%

Changes in Human In vivo Serotonin and Dopamine Transporter Availabilities during Chronic Antidepressant Administration

Kugaya

Seneca

Snyder

et al. 2002

Neuropsychopharmacol

152

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“…But do endogenous neurotransmitters still have an influence on radiolabelled b-CIT binding? Binding characteristics of [ 123 I]b-CIT in rat brain have been shown to be altered by serotonin transporter inhibitor clomipramine (Fujita et al 1997) and by opiate agonist fentanyl as well as by N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 (Nakano et al 1998). The release of dopamine from nigrostriatal axon terminals in the striatum is affected by stimulation of NMDA receptors, which provides support for the suggestion that these receptors are located on presynaptic nerve terminals and are able to influence transmitter release (Vizi 2000).…”

Section: Dopamine Transporter In Vivo Imagingmentioning

confidence: 99%

Dopamine Transporter in vitro Binding and in vivo Imaging in the Brain

Bergström¹,

Tupala²,

Tiihonen³

2001

Pharmacology & Toxicology

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Much research interest has lately been focused on the dopamine transporter function in brain. Recent findings indicate that dopamine reuptake is more like a highly regulated than a constitutive determinant of dopamine clearance. Positron emission tomography (PET) and single-photon emission tomography (SPET) offer unique methods to study dopamine transporter function. Results from in vivo PET and SPET studies correspond well with in vitro studies performed on post mortem human brain tissue. Considering some of the variances between in vitro and in vivo receptor binding phenomena it may be that the role of a compound to alter binding to monoamine uptake sites in vitro does not indicate its potential to affect monoamine transporters after administration in vivo. This discrepancy may be better understood taking into account recent studies indicating the possibility of a rapid regulation of transporter function and surface expression. Furthermore, the dopamine transporter is a fruitful target for CNS drug discovery. Fundamental nature of drug actions in vivo may be studied using demonstrated in vitro and in vivo imaging methods.

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“…This hypothesis was drawn from the b-CIT study by Fujita et al (1997), in which the binding potential of SERT in the hypothalamus in rat brain after administration of clomipramine was decreased to 35% of the control value. Thus, the present study is to our knowledge the first in vivo visualization of the effect of the serotonin reuptake inhibitor, clomipramine, in patients with OCD by means of b-CIT and SPECT.…”

Section: Introductionmentioning

confidence: 99%

Changes in Thalamus–Hypothalamus Serotonin Transporter Availability during Clomipramine Administration in Patients with Obsessive–Compulsive Disorder

Zitterl

Aigner

Stompe

et al. 2008

Neuropsychopharmacol

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To the authors' knowledge there is as of yet no study demonstrating in vivo alterations in human serotonin transporters (SERT) during clomipramine treatment in patients with obsessive-compulsive disorder. The only study in which SERT binding has been investigated in obsessive-compulsive disorder (OCD) patients before and after treatment is a small pilot study by Stengler-Wenzke et al (2006), who treated five OCD patients with citalopram. In the study at hand, we measured transporter availability in the thalamus-hypothalamus with [ 123 I] b-CIT single photon emission computed tomography (SPECT) in 24 patients with DSM-IV OCD. All patients displayed prominent behavioral checking compulsions (OC-checkers). At baseline and upon medication after 12 weeks of treatment with clomipramine (150 mg daily) 24 non-depressed OC-checkers underwent a SPECT measurement of brain SERT availability using [ 123 I]-2b-carbomethoxy-3b-(4-iodophenyl)tropane. For quantification of brain serotonin transporter availability, a ratio of specific to nondisplaceable [ 123 I] b-CIT brain binding was used (BP ND ¼ (thalamus and hypothalamusÀcerebellum)/cerebellum). The SERT availability was compared between baseline and after treatment and correlated with severity of OC symptomatology and treatment response as assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). After treatment with clomipramine patients showed a 48% reduced brain serotonin transporter availability in the thalamus-hypothalamus, as compared with values at baseline (0.72±0.12 vs 1.39±0.18, po0.001). Correlations between brain SERT availability and OC symptomatology (Y-BOCS scores) revealed significantly negative associations both at baseline and after treatment (r ¼ À0.46; po0.05 and r ¼ À0.53; po0.01 respectively). These data suggest that the SERT availability values could be considered a biological indicator of disease severity. Moreover, in search of predictors we found that higher pretreatment SERT availability significantly predicted better treatment response 12 weeks later (B ¼ 14.145 ± 4.514; t ¼ 3.133; p ¼ 0.005). These results provide further support for an important role of alterations in serotonergic neurons in the pathophysiology of OCD.

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

Cited by 8 publications

References 0 publications

Changes in Human In vivo Serotonin and Dopamine Transporter Availabilities during Chronic Antidepressant Administration

Changes in Human In vivo Serotonin and Dopamine Transporter Availabilities during Chronic Antidepressant Administration

Dopamine Transporter in vitro Binding and in vivo Imaging in the Brain

Changes in Thalamus–Hypothalamus Serotonin Transporter Availability during Clomipramine Administration in Patients with Obsessive–Compulsive Disorder

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