Fluvoxamine enhances prefrontal dopaminergic neurotransmission in adrenalectomized/castrated mice via both 5-HT reuptake inhibition and σ1 receptor activation

Ago, Yukio; Yano, Koji; Hiramatsu, Naoki; Takuma, Kazuhiro; Matsuda, Takehisa

doi:10.1007/s00213-011-2293-5

Cited by 26 publications

(23 citation statements)

References 54 publications

(56 reference statements)

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“…The neuronal-activity-marker c-Fos was determined 2 h after the encounter in the brains of male group-and isolation-reared mice, as described previously (Ago et al, 2011;Koda et al, 2010). Mice that were not exposed to an intruder were used as controls (Figure 2).…”

Section: C-fos Immunohistochemistrymentioning

confidence: 99%

“…Four independent sections per animal containing the prefrontal cortex, nucleus accumbens, amygdala, dorsal raphe nucleus, or ventral tegmental area were selected. Then, c-Fos-positive nuclei were counted manually by experienced observers blinded to the rearing and encounter conditions of the animals, under bright-field illumination using a Keyence microscope (BIOREVO, BZ-9000) (Ago et al, 2011;Koda et al, 2010). The number of c-Fos-positive nuclei in each section was determined in a 500 Â 500 mm 2 area in the left and right hemispheres and averaged using an ImageJ 1.41 software package (NIH, Bethesda, MD, USA).…”

Section: C-fos Immunohistochemistrymentioning

confidence: 99%

“…Postoperative analgesia was a single injection of buprenorphine (0.1 mg/kg, i.p. ; Ago et al, 2008Ago et al, , 2011. The active probe membranes were 3-and 1-mm long in the prefrontal cortex and nucleus accumbens, respectively.…”

Section: In Vivo Microdialysismentioning

confidence: 99%

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Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Ago

Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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Isolation-reared male rodents show abnormal behaviors such as hyperlocomotion, aggressive behaviors, deficits of prepulse inhibition, and depression-and anxiety-like behaviors, but the neurochemical mechanism for the effects of psychological stress in these animals is not fully understood. This study examined the effects of social interactions between isolation-reared mice and intruder mice on brain monoaminergic systems. A cage was divided into two compartments by a mesh partition to prevent direct physical interactions. The 20-min encounter with an intruder elicited a restless and hyperexcitable state (hyperactivity) in male, but not in female, isolationreared mice, whereas encounters with a sleeping intruder or a novel object did not. Although the encounter did not affect prefrontal neuronal-activity-marker c-Fos expression, dopamine (DA) levels, or serotonin (5-HT) levels in male group-reared mice or female isolation-reared mice, it increased prefrontal c-Fos expression, DA levels, and 5-HT levels in male isolation-reared mice. Furthermore, encounter-induced increases in c-Fos expression in the dorsal raphe nucleus and ventral tegmental area, but not in the nucleus accumbens shell, were much greater in isolation-reared than group-reared male mice. A 5-HT 1A receptor agonist, a metabotropic glutamate 2/3 receptor agonist, and a gamma-aminobutyric acid A receptor agonist attenuated isolation-induced aggressive behaviors and encounter-induced hyperactivity, c-Fos expression in the prefrontal cortex and dorsal raphe nucleus, and increases in prefrontal 5-HT levels. These findings suggest that the prefrontal DA and 5-HT systems are activated by encounter stimulation in male isolationreared mice, and the encounter-induced activation of 5-HT system triggers the induction of some abnormal behaviors in male isolation-reared mice. Furthermore, this study implies that the encounter stimulation-induced signal has a pharmacological significance.

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Section: C-fos Immunohistochemistrymentioning

confidence: 99%

Section: C-fos Immunohistochemistrymentioning

confidence: 99%

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Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Ago

Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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“…The significance of sigma-1 receptors for the antidepressant effect of fluvoxamine is still unclear, as under physiological conditions, a fluvoxamine induced increase in prefrontal cortex extracellular levels of 5-HT, dopamine and noradrenaline is independent on sigma-1 receptors [45].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the dopaminergic neurons have 5-HT receptors that permit the tonic control of dopamine release in the midbrain, striatum and nucleus accumbens [48]. It has been shown that systemic fluvoxamine administration induced a moderate increase in extracellular dopamine levels in the prefrontal cortex of rats [49] and mice [45], and the dorsal striatum of rats [50], but did not influence dopamine levels in the thalamus [50] of rats. The unchanged 5-HT synthesis rate in the nerve terminals following acute fluvoxamine administration could be explained by a fluvoxamine effect on extracellular dopamine levels at least in the area of dopaminergic nerve terminals like the striatum.…”

Section: Discussionmentioning

confidence: 99%

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

Mück‐Šeler

Pivac

Dikšić

2012

Nuclear Medicine and Biology

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Introduction-A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression.Methods-The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-14 C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 μCi).Results-There was no significant effect of fluvoxamine on plasma free tryptophan. After Benjamini-Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (−32%), but not in the median (−14%) and dorsal (−3%) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+41%) and ventral (+43%) hippocampus, visual (+38%), auditory (+65%) and parietal (+37%) cortex, and the substantia nigra pars compacta (+56%). There were no significant changes in the 5-HT synthesis rates in the median (+11%) and lateral (+24%) part of the caudate-putamen, nucleus accumbens (+5%), VTA (+16%) or frontal cortex (+ 6%).Conclusions-The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors. Keywords

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Plasma fluvoxamine levels and OCD symptoms/response in adult patients

Marazziti

Baroni

Giannaccini

et al. 2012

Human Psychopharmacology

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Objective In this study, we explored the possible relationships between plasma fluvoxamine levels and clinical features and/or response in adult obsessive–compulsive disorder (OCD) patients treated with this drug for 6 months. Methods Twenty OCD outpatients of both sexes who were already taking fluvoxamine (mean dose ± SD: 216.7 ±86.2) for at least 4 weeks were included in the study. The severity of OCD was assessed by means of the Yale–Brown obsessive–compulsive scale (Y‐BOCS). The fluvoxamine plasma levels were measured by high‐performance liquid chromatography analysis. All evaluations were performed after 4 weeks (t1) and 6 months (t2) of fluvoxamine intake. Results The plasma levels of fluvoxamine remained stable at the two assessment times, with no sex‐related differences. Sixteen (80%) patients responded to treatment as shown by the significant (>35%) decrease of the Y‐BOCS total score. Men's compulsions improved more than those of women. Significant and positive correlations were detected between fluvoxamine plasma levels at t1 and t2 and the difference (delta) of the Y‐BOCS total and compulsion subscale scores between t1 and t2. Another significant, albeit negative, correlation was measured between the difference of the compulsion subscale score and the difference of fluvoxamine levels at t1 and t2. Conclusions These findings underline the potential importance of evaluating fluvoxamine plasma levels in OCD and their relationships with the clinical response that may be gender‐related on specific symptoms. Copyright © 2012 John Wiley & Sons, Ltd.

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Fluvoxamine enhances prefrontal dopaminergic neurotransmission in adrenalectomized/castrated mice via both 5-HT reuptake inhibition and σ1 receptor activation

Abstract: These findings suggest that fluvoxamine enhances prefrontal dopaminergic neurotransmission via both 5-HT reuptake inhibition and σ(1) receptor activation under the circulating neuroactive steroid-deficient conditions.

Cited by 26 publications

References 54 publications

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

Plasma fluvoxamine levels and OCD symptoms/response in adult patients

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