Impact of Ovarian Hormones on the Modulation of the Serotonin Transporter by Fluvoxamine

Benmansour, Saloua; Piotrowski, Jonathan P; Altamirano, Alfonso; Frazer, Alan

doi:10.1038/npp.2008.23

Cited by 41 publications

(55 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interactions between the muscarinic cholinergic and serotonergic systems are hypothesized to contribute to the pathogenesis of major depression (Overstreet et al, 1996(Overstreet et al, , 1998. Multiple aspects of serotonergic system function are influenced by testosterone, progesterone, and/or estrogen, and these interactions are hypothesized to underlie sex differences in the clinical epidemiology and course of mood disorders (Benmansour et al, 2009;Gupta et al, 2007;Rubinow et al, 1998;Sell et al, 2008;Zhang et al, 2006). Such interactions conceivably may influence cholinergic-serotonergic interactions in a way that modulates antidepressant responses to scopolamine.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, biological theories suggest that differences in brain structure and/or function underlie the difference in prevalence. For example, estrogen and progesterone may influence depressive symptoms in women as these hormones modulate levels of serotonin, norepinephrine, acetylcholine, and monoamine oxidase (Benmansour et al, 2009;Gupta et al, 2007;Sell et al, 2008;Zhang et al, 2006). Further evidence for the implication of these hormones in depression comes from studies showing that the incidence of depression is greater in women than in men during the reproductive years, but after menopause when levels of estrogen and progesterone remain low, the incidence of depression in women becomes less than that seen in men (Bebbington et al, 1998;Bland et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Furey

Khanna

Hoffman

et al. 2010

Neuropsychopharmacol

105

View full text Add to dashboard Cite

Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 mg/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group Â block interaction (F ¼ 21.0, po0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F ¼ 8.4, p ¼ 0.006). The treatment group Â block interaction was also significant in males (F ¼ 3.8, p ¼ 0.043) and females (F ¼ 35.6, po0.001) separately. A block Â gender interaction (F ¼ 7.4, p ¼ 0.009) indicated that the response magnitude was larger in women. The treatment Â block interaction was significant for the HAM-A across gender (F ¼ 12.0, po0.001), and was significant for females (F ¼ 24.9, po0.001) but not for males (F ¼ 1.3, p ¼ 0.30). When comparing the baseline block to study end, the block Â gender interaction (F ¼ 12.6, p ¼ 0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Furey

Khanna

Hoffman

et al. 2010

Neuropsychopharmacol

105

View full text Add to dashboard Cite

show abstract

“…Both acute administration of 17β-estradiol in the CA3 region of the hippocampus and systemic administration of estradiol benzoate cause slowing of the 5-HT clearances, as well as an inhibition of the ability of luvoxamine to slow the clearance of 5-HT [41]. These efects are mediated by estrogen receptors α and β.…”

Section: Preclinical Studies Of Serotonergic Changes Associated With mentioning

confidence: 99%

“…Benmansour and collaborators' research group [41] has explored the signaling mechanisms involved in the interaction of estradiol and serotonergic systems in rats. Both acute administration of 17β-estradiol in the CA3 region of the hippocampus and systemic administration of estradiol benzoate cause slowing of the 5-HT clearances, as well as an inhibition of the ability of luvoxamine to slow the clearance of 5-HT [41].…”

Section: Preclinical Studies Of Serotonergic Changes Associated With mentioning

confidence: 99%

Depression and Serotonergic Changes during the Climacteric and Postmenopausal Stages: Hormonal Influences

García-Ríos¹,

Mora-Perez²,

Soria-Fregozo³

2017

A Multidisciplinary Look at Menopause

View full text Add to dashboard Cite

Depression is a psychiatric disorder that afects a high percentage of women. Most of the depression disorders turn up during the premenopause and perimenopause stages when the hormonal oscillations make an impact in the brain function principally on the serotonergic system, which is related to neurobiology of depression. 5-HT1A and 5-HT2A receptors change on functionality and density in aferent areas related to emotional modulation and increased serotonin clearance, and the binding potential of serotonin transport has been related to the underlying mechanism of the depression during the climacteric or postmenopausal stage. Some indings have been proven on preclinical studies. These studies on animals have recognized how estrogen treatment activates intracellular signaling pathways as mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK), tyrosine kinase brain-derived neurotrophic factor receptor (TrKB), insulin-like growth factor-1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3)/serine/threonine-speciic protein kinase (Akt), and metabotropic glutamate receptor 1 (mGluR1) which interact with the serotonergic system to allow establishment of the estradiol efects on mood regulation. Thus, the interaction between the woman's reproductive status and the serotonin changes could be useful to create prevention strategies, early diagnosis, and medical treatment of climacteric and postmenopausal women with depression, in order to improve their quality of life.

show abstract

“…In addition, SSRIs are an excellent treatment for premenstrual dysphoria disorder. Thus, the report by Benmansour et al (2008) demonstrating a sex specific effect of estradiol and progesterone on function of the serotonin transporter is quite important. However, the effect is the opposite of what would be predicted from the clinical literature, further underscoring the complexity of understanding the interactions between ovarian hormones and serotonin systems.…”

mentioning

confidence: 99%

Perspective: Sex Matters: Gonadal Steroids and the Brain

Young

Becker

2009

Neuropsychopharmacol

View full text Add to dashboard Cite

Sex matters to every cell of the body and thus gonadal steroids have the capability of affecting numerous behaviors and neurotransmitters. Several reports in this issue highlight the importance of gonadal steroids: estradiol and progesterone modulate the serotonin transporter in rodents changes in D2 receptors across the menstrual cycle in female cynomolgus monkeys testosterone influences amygdala reactivity in women and temporary suppression of gonadal steroids influences sexual in both men and women. This body of work challenges all of neuropsychopharmacology to consider the importance of sex and gonadal steroids in future studies. Neuropsychopharmacology (2009) 34, 537-538; doi:10.1038/npp.2008 Sex matters to every cell of the body (Wizemann and Pardue, 2001). Despite this conclusion by the IOM, the area of sex and gonadal hormones is frequently ignored in the field of neuropsychopharmacology and other basic biomedical fields. This is to a large extent because of the difficulty of parsing the roles of chromosomal sex, gonadal sex, and gonadal steroid hormones (Becker et al, 2005). Nevertheless, these are factors that are increasingly important to address, as evidenced by the articles in this issue of Neuropsychopharmacology. In this issue of Neuropsychopharmacology the importance of sex/gender differences in the brain as well as the effects of steroid hormones on brain function are examined from the perspective of psychiatric disorders, the neurological basis of sexual behavior and neurotransmitter receptor/ transporter function.Depression is more common in women, and women appear to respond better to SSRIs than men (Kornstein et al, 2000;Young et al, 2008). In addition, SSRIs are an excellent treatment for premenstrual dysphoria disorder. Thus, the report by Benmansour et al (2008) demonstrating a sex specific effect of estradiol and progesterone on function of the serotonin transporter is quite important. However, the effect is the opposite of what would be predicted from the clinical literature, further underscoring the complexity of understanding the interactions between ovarian hormones and serotonin systems. Perhaps these findings help us to better understand the vulnerability to mood disorders at times when estradiol and progesterone are high, such as the luteal phase of the menstrual cycle. Of note is the fact that these changes in response to estradiol and progesterone were not observed in hippocampi of male rats, underscoring the importance of sexual differentiation of the brain on the effects of gonadal steroids.Studying nonhuman primates with PET imaging of D2 receptors, Czoty et al (2008) found that [18F]FCP binding sites showed a greater availability in the caudate and putamen during the luteal phase, suggesting more unoccupied receptors during this menstrual cycle phase. Although the changes might be due to increased numbers of receptors, the use of a ligand displaceable by endogenous DA suggests the alternative possibility that higher receptor availability reflects decreased DA release during...

show abstract

Impact of Ovarian Hormones on the Modulation of the Serotonin Transporter by Fluvoxamine

Cited by 41 publications

References 60 publications

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Scopolamine Produces Larger Antidepressant and Antianxiety Effects in Women Than in Men

Depression and Serotonergic Changes during the Climacteric and Postmenopausal Stages: Hormonal Influences

Perspective: Sex Matters: Gonadal Steroids and the Brain

Contact Info

Product

Resources

About