Effects Of Serotonin Reuptake Inhibitors Research Articles

Serotonin Reuptake Inhibitor Increases Pseudarthrosis Rates in Anterior Cervical Discectomy and Fusions.

Retrospective cohort. To determine (1) the effects of serotonin reuptake inhibitors in pseudarthrosis rates after anterior cervical decompression and fusion (ACDF) and (2) to identify patient-reported outcome measures in patients taking serotonin reuptake inhibitors. Recent literature suggests that selective serotonin reuptake inhibitors (SSRIs) may inhibit fracture healing via downregulation of osteoblast differentiation. Spinal fusion supplementation with osteoblast-rich substances enhances spinal fusion, thus SSRIs may be detrimental. Patients with 1-year postoperative dynamic cervical spine radiographs following ACDF were grouped into serotonin reuptake inhibitor prescriptions (SSRI, serotonin-norepinephrine reuptake inhibitor [SNRI], or tricyclic antidepressant [TCA]) and no prescription (atypical antidepressant or no antidepressant). Pseudarthrosis was defined as ≥1 mm interspinous process motion on dynamic radiographs. Logistic regression models were controlled for confounding to analyze pseudarthrosis rates. Alpha was set at p - values of <0.05. Of the 523 patients who meet the inclusion criteria, 137 (26.2%) were prescribed an SSRI, SNRI, or TCA. Patients with these prescriptions were more likely to have pseudarthrosis (p =0.008) but not a revision surgery due to pseudarthrosis (p =0.219). Additionally, these patients had worse 1-year postoperative mental component summary (MCS)-12 (p =0.015) and Neck Disability Index (NDI) (p =0.006). The multivariate logistic regression analysis identified SSRI/SNRI/TCA use (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.11-2.99; p =0.018) and construct length (OR, 1.91; 95% CI, 1.50-2.44; p <0.001) as pseudarthrosis predictors. A SSRI/SNRI/TCA prescription was a revision surgery predictor due to adjacent segment disease on univariate analysis (OR, 2.51; p =0.035) but not on multivariate logistic regression analysis (OR, 2.24; p =0.10). Patients taking serotonin reuptake-inhibiting antidepressants are at increased risk of worse postoperative outcome scores, including NDI and MCS-12, likely due to their underlying depression. This may contribute to their greater likelihood of having adjacent segment surgery. Additionally, preoperative use of serotonin reuptake inhibitors in patients undergoing an ACDF is a predictor of radiographic pseudarthrosis but not pseudarthrosis revision.

Hypomethylation of monoamine oxidase A promoter/exon 1 region is associated with temper outbursts in Prader-Willi syndrome

BackgroundPrader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by the absence of paternally expressed and maternally imprinted genes on chromosome 15q 11.2–13. It is associated with a certain behavioural phenotype, especially temper outbursts with verbal and physical aggression towards others. Recent studies show a promising therapeutic effect of serotonin reuptake inhibitors like sertraline on frequency and intensity of outbursts. Monoamine oxidase A (MAOA) (X p11.23) plays a crucial role in the metabolism of monoamines. Dysregulation in methylation of the CpG island spanning the promoter region and exon 1 of MAOA is implicated in impulsive and aggressive behaviour. MethodsIn the present study, methylation rates of CpG dinucleotides in the MAOA promoter and exon 1 region were determined from DNA derived from whole blood samples of PWS patients (n = 32) and controls (n = 14) matched for age, sex and BMI via bisulfite sequencing. PWS patients were grouped into those showing temper outbursts, and those who do not. ResultsOverall, PWS patients show a significant lower methylation rate at the promoter/exon 1 region than healthy controls in both sexes. Furthermore, PWS patients, male as well female with temper outbursts show a significant lower methylation rate than those without temper outbursts (p < 0.001 and p = 0.006). ConclusionThe MAOA promoter/exon 1 region methylation seems to be dysregulated in PWS patients in sense of a hypomethylation, especially in those suffering from temper outbursts. This dysregulation probably plays a crucial role in the pathophysiology of temper outbursts in PWS.

Fluoxetine administration in juvenile overfed rats improves hypothalamic mitochondrial respiration and REDOX status and induces mitochondrial biogenesis transcriptional expression

Nutritional imbalance in early life may disrupt the hypothalamic control of energy homeostasis and increase the risk of metabolic disease. The hypothalamic serotonin (5-hydroxytryptamine; 5-HT) system based in the hypothalamus plays an important role in the homeostatic control of energy balance, however the mechanisms underlying the regulation of energy metabolism by 5-HT remain poorly described. Several crucial mitochondrial functions are altered by mitochondrial stress. Adaptations to this stress include changes in mitochondrial multiplication (i.e, mitochondrial biogenesis). Due to the scarcity of evidence regarding the effects of serotonin reuptake inhibitors (SSRI) such as fluoxetine (FLX) on mitochondrial function, we sought to investigate the potential contribution of FLX on changes in mitochondrial function and biogenesis occurring in overfed rats. Using a neonatal overfeeding model, male Wistar rats were divided into 4 groups between 39 and 59 days of age based on nutrition and FLX administration: normofed + vehicle (NV), normofed + FLX (NF), overfed + vehicle (OV) and overfed + FLX (OF). We found that neonatal overfeeding impaired mitochondrial respiration and increased oxidative stress biomarkers in the hypothalamus. FLX administration in overfed rats reestablished mitochondrial oxygen consumption, increased mitochondrial uncoupling protein 2 (Ucp2) expression, reduced total reactive species (RS) production and oxidative stress biomarkers, and up-regulated mitochondrial biogenesis-related genes. Taken together our results suggest that FLX administration in overfed rats improves mitochondrial respiratory chain activity and oxidative balance and increases the transcription of genes employed in mitochondrial biogenesis favoring mitochondrial energy efficiency in response to early nutritional imbalance.

Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?

Selective serotonin reuptake inhibitor (SSRI) drugs, targeting serotonin transport, are widely used. A puzzling and biomedically important phenomenon concerns the persistent sexual dysfunction following SSRI use seen in some patients. What could be the mechanism of a persistent physiological state brought on by a transient exposure to serotonin transport blockers? In this study, we briefly review the clinical facts concerning this side effect of serotonin reuptake inhibitors and suggest a possible mechanism. Bioelectric circuits (among neural or non-neural cells) could persistently maintain alterations of bioelectric cell properties (resting potential), resulting in long-term changes in electrophysiology and signaling. We present new data revealing this phenomenon in planarian flatworms, in which brief SSRI exposures induce long-lasting changes in resting potential profile. We also briefly review recent data linking neurotransmitter signaling to developmental bioelectrics. Further study of tissue bioelectric memory could enable the design of ionoceutical interventions to counteract side effects of SSRIs and similar drugs.

Сочетание стрессовых воздействий в критические периоды развития повышает устойчивость к стрессу воспалительной боли у взрослых крыс

We studied the long-term effect of the combination of stress in the prenatal and prepubertal periods of development on indicators of tonic inflammatory pain in the formalin test and the depressive-like behavior, as well as on the stress reactivity of the hormonal response in adult rats. In addition, in rats of both sexes, the effect of serotonin reuptake inhibitor (5-HT) fluoxetine and 5-HT1A agonist buspirone, chronically administered to their stressed mothers during pregnancy, on the studied types of adaptive behavior disturbed by prenatal stress was evaluated. It was found that in rats of both sexes, prenatal stress intensified the pain response organized at the spinal and supraspinal levels of the central nervous system, fluoxetine and buspirone normalized them. Stress in the prepubertal period of development leveled the effect of prenatal stress on the inflammatory pain response integrated at the supraspinal level in adult rats; under these conditions, fluoxetine and buspirone did not act, unlike their antinociceptive effect on the pain response integrated at the spinal level. Stress in prepubertal age leveled the sex differences found in the depressive-like behavior in prenatally non-stressed and prenatally stressed rats with saline. In control adult females and adult females with prenatal effects, prepubertal stress increased plasma corticosterone after forced swimming compared to basal hormone levels, but no significant differences in the level of stress reactivity of the hormonal response after forced swimming were found. Thus, the conditions of stressful impacts that increase resistance to stress in adult rats are identified. Stress in critical periods of development forms a phenotype with increased stress resistance to inflammatory pain, which was found in the response organized at the supraspinal level in adults.

Antidepressant effect of the interaction of fluoxetine with granisetron.

Selective serotonin reuptake inhibitors (SSRIs) may produce digestive side effects such as nausea and vomiting, diarrhoea and decreased appetite. These side effects are determined by the increase in serotonin availability at 5-HT3 receptors. Granisetron, a serotonin 5-HT3 receptor antagonist, is expected to antagonize the digestive adverse effects of serotonin reuptake inhibitors, but the question is to what extent granisetron influences the antidepressant effect of these substances. The aim of this study was to determine the dose of fluoxetine that has an antidepressant effect in the Porsolt test, and the interaction between fluoxetine and granisetron with respect to the antidepressant effect in this test. In experiment 1, fluoxetine was antidepressant only at 20 mg/kg body weight (bw). In experiment 2, granisetron 1 mg/kg bw had a statistically significant antidepressant effect vs. control. Fluoxetine 20 mg/kg bw associated with a small dose of granisetron (0.1 mg/kg bw) produced a significant antidepressant effect vs. control. This shows that low doses of granisetron associated to fluoxetine might produce a significant antidepressant effect, suggesting a potentiation between these two drugs used in sub-effective antidepressant doses. In conclusion, in our experimental conditions, we can assume that granisetron in low doses could be used to combat intestinal transit disorders produced by SSRI antidepressants. These low doses are preferred, because they increase the antidepressant effect of these SSRIs.

A review of the antimicrobial side of antidepressants and its putative implications on the gut microbiome.

Serotonin reuptake inhibitors are the predominant treatment for major depressive disorder. In recent years, the diversity of the gut microbiota has emerged to play a significant role in the occurrence of major depressive disorder and other mood and anxiety disorders. Importantly, the role of the gut microbiota in the treatment of such disorders remains to be elucidated. Here, we provide a review of the literature regarding the effects of physiologically relevant concentrations of serotonin reuptake inhibitors on the gut microbiota and the implications this might have on their efficacy in the treatment of mood disorders. First, an estimation of gut serotonin reuptake inhibitor concentrations was computed based on pharmacokinetic and gastrointestinal transit properties of serotonin reuptake inhibitors. Literature regarding the in vivo and in vitro antimicrobial properties of serotonin reuptake inhibitors was gathered, and the estimated gut concentrations were examined in the context of these data. Computer-based investigation revealed putative mechanisms for the antimicrobial effects of serotonin reuptake inhibitors. In vivo evidence using animal models shows an antimicrobial effect of serotonin reuptake inhibitors on the gut microbiota. Examination of the estimated physiological concentrations of serotonin reuptake inhibitors in the gastrointestinal tract collected from in vitro studies suggests that the microbial community of both the small intestine and the colon are exposed to serotonin reuptake inhibitors for at least 4 hours per day at concentrations that are likely to exert an antimicrobial effect. The potential mechanisms of the effect of serotonin reuptake inhibitors on the gut microbiota were postulated to include inhibition of efflux pumps and/or amino acid transporters. This review raises important issues regarding the role that gut microbiota play in the treatment of mood-related behaviours, which holds substantial potential clinical outcomes for patients suffering from major depressive disorder and other mood-related disorders.

The effect of serotonin reuptake inhibitors on the vaginal epithelium in postmenopausal women

Purpose: Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are used as alternative treatments for the vasomotor symptoms of menopause in women who are unwilling or unable to receive hormone therapy. These agents have been associated with sexual dysfunction and xerostomia (dry mouth), but the effect on the vagina has not been studied. The objective of this study was to determine the effect of SSRIs and SNRIs on the vaginal epithelium and sexual function in postmenopausal women, using both subjective and objective measures.Materials and methods: A cross-sectional study of postmenopausal women not using any local or systemic estrogen therapy was conducted. The main outcomes included the Female Sexual Function Index (FSFI), vaginal epithelial maturation index (MI), and pH.Results: Sixty-six women were recruited, 30 using SSRIs/SNRIs and 36 who were not (control). Both the proportion of superficial vaginal epithelial cells and the total MI were higher in the SSRI/SNRI group (p = 0.006 and p = 0.047, respectively). There were no significant differences in FSFI scores, vaginal pH, or total MI values.Conclusion: The use of serotonin reuptake inhibiting drugs does not appear to have a negative influence on the vaginal epithelium and associated vaginal atrophy.

Pharmacokinetics of serotonergic drugs: focus on OCD

ABSTRACTIntroduction: Although the treatment of obsessive-compulsive disorder (OCD), a common, chronic, and disabling psychiatric condition, has significantly improved in the last decades, with the demonstration of the specific effectiveness of serotonin reuptake inhibitors (SRIs), a large proportion of patients still show high relapse rates. In addition, pharmacological treatments should be maintained for years, so that the clinicians should take into account the pharmacokinetic changes in the long-term, which may be responsible for dangerous side effects or interactions.Areas covered: The aim of this paper was to review the literature on the pharmacokinetics of SSRIs and clomipramine, and on their pharmacokinetic parameters in OCD patients.Expert opinion: Although the literature on the pharmacokinetics of both clomipramine and SSRIs is consistent, data on pharmacokinetic parameters in OCD patients are very few. Given the impact of OCD, its chronicity requiring long-term treatments, together with the need to increase the clinical response rate, more studies in this field are urgently required.

Escitalopram attenuates fear stress-induced increase in amygdalar dopamine following methamphetamine-induced sensitisation: Implications of fine-tuning action of selective serotonin reuptake inhibitors on emotional processing

Serotonin reuptake inhibitors modulate the serotonergic pathways of the nervous system and are widely used for treating psychiatric conditions such as anxiety and depression. The dopaminergic system is related to the development of these conditions. Previous studies on methamphetamine-sensitised rats (behavioural models of stress vulnerability) have shown increased release of dopamine in response to conditioned stress in the amygdala. This biochemical abnormality was proposed to underlie the pathophysiology of stress vulnerability. However, the effect of serotonin reuptake inhibitors on dopamine levels and its consequent impact on emotional processing is unclear. Here we examined the acute effect of escitalopram, a highly selective serotonin reuptake inhibitor, on fear-related behaviour, baseline dopamine release and dopamine release in response to conditioned fear stress in the amygdala of model rats. Male Sprague-Dawley rats received 2 mg/kg/day, s.c. of methamphetamine for 10 days to sensitise them to the drug, and a fear conditioning paradigm was instituted to model psychological stress. Dopamine changes in the amygdala in response to systemic administration of escitalopram followed by conditioned fear stress were measured using microdialysis and high-performance liquid chromatography. Baseline dopamine release in the amygdala was increased by escitalopram in non-sensitised rats but not in methamphetamine-sensitised rats. Escitalopram attenuated dopamine release in response to the fear-conditioned stimulus in both sensitised and non-sensitised rats. The extent of suppression in methamphetamine-sensitised rats (− 90%) was greater than that in non-sensitised rats (− 48%). These findings suggest that serotonin reuptake inhibitors indirectly stabilise the dopaminergic pathway and modulate emotional processing in the amygdala.

The Effect of Serotonin Reuptake Inhibitors on the Genitourinary Syndrome of Menopause

The Effect of Serotonin Reuptake Inhibitors on the Genitourinary Syndrome of Menopause

Chronic Intake of the Selective Serotonin Reuptake Inhibitor Fluoxetine Enhances Atherosclerosis.

Cardiovascular diseases and depression are the leading causes of disability in Western countries. Clinical data on potential cardiovascular effects of serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressant drugs, are controversial. In addition to blocking serotonin reuptake transporter in the brain, SSRIs deplete the major peripheral serotonin (5-hydroxytryptamine [5-HT]) storage by inhibiting serotonin reuptake transporter-mediated uptake in platelets. In this study, we aimed to investigate the effect of chronic SSRI intake on the development of atherosclerosis. Treatment of apolipoprotein E-deficient mice with the SSRI fluoxetine for 2, 4, or 16 weeks increased atherosclerotic lesion formation, with most pronounced effect during early plaque development. Intravital microscopy of carotid arteries revealed enhanced myeloid cell adhesion on fluoxetine treatment. Mechanistically, we found that fluoxetine augmented vascular permeability and increased chemokine-induced integrin-binding activity of circulating leukocytes. In vitro stimulation of murine blood demonstrated that fluoxetine, but not 5-HT, could directly promote β1 and β2 integrin activation provided C-C motif chemokine ligand 5 was also present. Similar effects were observed with the SSRI escitalopram. Enhanced C-C motif chemokine ligand 5-induced integrin activation by fluoxetine was also confirmed in a human neutrophil-like cell line. In contrast to the proatherogenic properties of fluoxetine, pharmacological inhibition of the peripheral 5-HT synthesizing enzyme tryptophan hydroxylase 1 did not promote atherosclerosis, suggesting that the proatherogenic effect of fluoxetine occurs independent of peripheral 5-HT depletion. SSRI intake may promote atherosclerosis and therefore potentially increase the risk for acute cardiovascular events by a mechanism that is independent of 5-HT depletion.

Medicaments and oral healthcare 5. Adverse effects of -medications and over-the-counter drugs on teeth

Intrinsic tooth discoloration may occur as an adverse effect of fluoride and tetracyclines. Extrinsic tooth discoloration may occur as superficial staining or as discoloration of the superficial pellicle and/or biofilm due to chlorhexidine, liquid iron salts, essential oils, some antibiotics and stannous fluoride. Inhibition of orthodontic tooth movement has been reported due to the use of prostaglandin synthetase inhibitors. If medications or over-the-counter drugs induce hyposalivation or contain much sucrose, caries may develop. Erosion may occur if the acidity of medications or over-the-counter drugs is excessive. Attrition is a well-known adverse effect of serotonin reuptake inhibitors, antiparkinson agents, and antipsychotics. Congenital dysplasia is observed following childhood treatment with cytostatic drugs. External cervical root resorption is an adverse effect of internal teeth-whitening products. Prenatal exposure to antiepileptic drugs and childhood treatment with cytostatic drugs may cause dental agenesis. Antiseptic drugs applied for external teeth-whitening and toothpastes with additional ingredients to prevent extrinsic discoloration and creation of calculus, may cause tooth hypersensitivity.

P.2.f.041 - Net effect of serotonin reuptake inhibitors on suicidality in depression is beneficial rather than harmful already during the first week of treatment

P.2.f.041 - Net effect of serotonin reuptake inhibitors on suicidality in depression is beneficial rather than harmful already during the first week of treatment

Cannabidiol reverses the mCPP‐induced increase in marble‐burying behavior

Cannabidiol (CBD), one of the main components of Cannabis sp., presents clinical and preclinical anxiolytic properties. Recent results using the marble-burying test (MBT) suggest that CBD can also induce anticompulsive-like effects. Meta-chloro-phenyl-piperazine (mCPP) is a nonspecific serotonergic agonist (acting mainly at 5HT1A, 5HT2C and 5HT1D receptors) reported to increase symptoms in OCD patients and block the anticompulsive-like effect of serotonin reuptake inhibitors (SRIs) in animal models. The aim of this study was to investigate the interference of CBD on mCPP effects in repetitive burying. Administration of mCPP showed dual effects in the MBT, increasing the number of buried marbles at lower (0.1 mg/kg) while decreasing it at higher doses (1 mg/kg), an effect not related to a general increase in anxiety-like behavior. As found previously, CBD (30 mg/kg) and the positive control fluoxetine (FLX; 10 mg/kg) decreased burying behavior without changing general exploratory activity. A similar effect was found when subeffective doses of CBD (15 mg/kg) and FLX (3 mg/kg) were administered together. These subeffective doses alone were also able to block mCPP-induced repetitive burying. The results, in addition to reinforcing a possible anticompulsive effect of CBD, also suggest that mCPP-induced repetitive burying could be a useful test for the screening of compounds with presumed anticompulsive properties.

5-HT1A receptor as a key player in the brain 5-HT system

Among an impressive variety of identified serotonin receptors, 5-HT1A attracts particular attention due to its central role in the regulation of 5-HT-ergic neurotransmission and the data on its involvement in the mechanisms of stress response, aggressive behavior, anxiety, and depression. This review concentrates on the cross-regulation between 5-HT receptors and the implication of the 5-HT1A receptor in the genetic control of 5-HT-related behavior. Specifically, it describes the (1) functional interactions between 5-HT1A, 5-HT2A, 5-HT3, and 5-HT7 receptors; (2) cross-talk between 5-HT1A receptor and genes encoding key members of the brain 5-HT system; (3) implication of the 5-HT1A receptor in natural hibernation and genetic predisposition to different kinds of defensive behavior; and (4) role of 5-HT1A autoreceptors and heteroreceptors in anxiety, depression, and suicide, and in the antidepressant effect of serotonin reuptake inhibitors. This review provides converging lines of evidence that the 5-HT1A receptor contributes to the action of other 5-HT receptors, modulating their effect on behavior, and describes new data on the unique role of the 5-HT1A receptor in the indirect regulation of gene expression and in the autoregulation of the brain 5-HT system.

Modulation of Frontostriatal Interaction Aligns with Reduced Primary Reward Processing under Serotonergic Drugs

Recently, functional interactions between anteroventral prefrontal cortex and nucleus accumbens (NAcc) have been shown to relate to behavior counteracting reward-desiring (Diekhof and Gruber, 2010). Downregulation of the reward system by serotonin has also been suggested as the mode of action accounting for unsatisfactory effects of serotonin reuptake inhibitors (SSRIs) such as insufficient alleviation or even increase of anhedonia, and loss of interest. However, understanding of the in vivo mechanisms of SSRI-related alteration of the human reward system is still incomplete. Using functional magnetic resonance imaging (fMRI) within a double-blind cross-over within-subjects study design and administering the SSRI paroxetine, the dopamine/norepinephrine reuptake inhibitor bupropione, and placebo for 7 d each, we investigated a group of 18 healthy male subjects. Under paroxetine, subjects showed significantly decreased activation of the bilateral NAcc during processing of primary rewards (erotic videos), but not under bupropion. Similar to the previous study, analysis of psychophysiological interactions revealed that this downregulation relied on negative interactions between left and right NAcc fMRI signals and the bilateral anteroventral prefrontal cortex that now were significantly enhanced under paroxetine and reduced under bupropion. Individual drug-dependent modulations of interacting brain regions were significantly associated with individual expressions of impulsivity as a personality trait. Our results corroborate and extend previous insights on interregional crosstalk from secondary to primary rewards and demonstrate parallels between active inhibitory control of and serotonergic effects on the dopaminergic reward system's activity.

Identification and Treatment of Depression in Minority Populations

Depression is a common condition, representing close to 6% of visits to primary care providers. Although minorities are more likely to have chronic depression, they are more likely to be incorrectly diagnosed and less likely to receive treatment when compared to the mainstream population. Screening and appropriate treatment within primary care is recommended in clinical practices that have systems in place to assure accurate diagnosis, effective treatment, and follow-up. This recommendation is especially relevant for treatment of minority populations, as they are more likely to seek care for mental health problems from primary care providers rather than specialists. A number of self-report screening tools that simplify screening are available. Treatment modalities that are supported by evidence are psychotherapy, prescription medications, and electroconvulsive therapy for severe depression. Selective serotonin reuptake inhibitors (SSRIs) have become the cornerstone of therapy for depression since the Food and Drug Administration (FDA) approval of fluoxetine in 1987. No substantial differences in efficacy of SSRIs have been found, although data suggest differences with respect to onset of action and adverse effects that may be relevant in the choice of one medicine over another. Common side effects of serotonin reuptake inhibitors include nausea, diarrhea, insomnia, somnolence and dizziness, akathisia, and sexual dysfunction. While most of these symptoms tend to subside within several weeks of use, sexual dysfunction appears to be a long-term side effect that typically reverses within a few days after discontinuation of the causative medication. Selective norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, and tricyclic antidepressants (TCAs) are other commonly used medications. Complementary and alternative treatments, such as St. John's wort (Hypericum perforatum), exercise, acupuncture, music therapy, and relaxation, have limited data supporting their efficacy.

Effect of Serotonin Reuptake Inhibitors on Pulmonary Hemodynamics in Humans

BackgroundSerotonin promotes pulmonary arterial vasoconstriction and pulmonary arterial smooth muscle cell proliferation, thereby having the potential to increase pulmonary arterial blood pressure. Although serotonin reuptake inhibitors (SRIs) might inhibit further deterioration in patients with manifest pulmonary arterial hypertension, they may induce pulmonary hypertension in healthy newborns after fetal exposure. As it is unclear whether treatment with SRIs affects pulmonary hemodynamics in adults without pulmonary hypertension, the aim of the present study was to investigate the effect of SRIs on pulmonary hemodynamics in such subjects.MethodsSixteen patients with stable angina pectoris scheduled for first time coronary artery bypass grafting were included in the study. Of these 8 were currently treated with an SRI (the SRI group) and 8 were not (the control group). Pulmonary arterial pressures were measured before induction of anesthesia by means of a pulmonary artery catheter. Serotonin transporter and 5-HT2A receptor gene polymorphisms and platelet 5-HT2A receptor expression were studied to elucidate their possible role as modifying factors.ResultsNo patients in any of the groups had pulmonary arterial hypertension. Mean pulmonary artery pressure was 15.0 mmHg in the SRI group and 14.5 mmHg in the control group (P = 0.50; 95% confidence interval for the difference, -2.9 to +3.9 mmHg). Neither were there any significant differences between the groups for any of the other hemodynamic variables studied. The various gene polymorphisms and the extent of platelet 5-HT2A receptor expression did not influence the hemodynamic variables.ConclusionsSRI treatment did not significantly influence pulmonary hemodynamics in patients without pulmonary hypertension.KeywordsSerotonin; Selective serotonin reuptake inhibitors; Pulmonary hemodynamics; Pulmonary hypertension

Strain‐dependent serotonin neuron feedback control: role of serotonin2C receptors

We investigated the role of serotonin(2C) receptor-mediated feedback mechanisms in the response to citalopram in C57BL/6 and DBA/2 mice, which are respectively responders and non-responders to selective serotonin reuptake inhibitors in the forced swimming test. The microdialysis technique was used to assess changes in extracellular serotonin and GABA in the mouse dorsal raphé (DR). Citalopram (1.25-20 mg/kg) raised extracellular serotonin and GABA in the DR of both mouse strains. These effects were abolished by depleting brain serotonin with p-chlorophenylalanine (300 mg/kg × 3). Systemic and/or intra-DR infusion of the serotonin(2C) receptor antagonist 6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline (1 mg/kg and 0.1 μM, respectively) enhanced citalopram's effect on extracellular serotonin in the DR and medial prefrontal cortex and abolished the rise of GABA in the DR of DBA/2 mice but had no effect in C57BL/6 mice. The serotonin(2C) receptor agonist Ro60-0175 (0.03-3.0 mg/kg) reduced extracellular serotonin and raised GABA in the DR of DBA/2 mice but had much less effect in C57BL/6 mice. These findings show that the sensitivity of serotonin(2C) receptors determines the efficacy of augmentation strategies aimed at enhancing the effect of serotonin reuptake inhibitors on extracellular serotonin through the suppression of serotonin(2C) receptor-mediated feedback control of serotonin neurons.