Fluoxetine Treatment Research Articles

Exercise more efficiently regulates the maturation of newborn neurons and synaptic plasticity than fluoxetine in a CUS-induced depression mouse model

Depression, a common and important cause of morbidity and mortality worldwide, is commonly treated with antidepressants, electric shock and psychotherapy. Recently, increasing evidence has shown that exercise can effectively alleviate depression. To determine the difference in efficacy between exercise and the classic antidepressant fluoxetine in treating depression, we established four groups: the Control, chronic unpredictable stress (CUS/STD), running (CUS/RUN) and fluoxetine (CUS/FLX) groups. The sucrose preference test (SPT), the forced swimming test (FST), the tail suspension test (TST), immunohistochemistry, immunofluorescence and stereological analyses were used to clarify the difference in therapeutic efficacy and mechanism between exercise and fluoxetine in the treatment of depression. In the seventh week, the sucrose preference of the CUS/RUN group was significantly higher than that of the CUS/STD group, while the sucrose preference of the CUS/FLX group did not differ from that of the CUS/STD group until the eighth week. Exercise reduced the immobility time in the FST and TST, while fluoxetine only reduced immobility time in the TST. Hippocampal structure analysis showed that the CUS/STD group exhibited an increase in immature neurons and a decrease in mature neurons. Exercise reduced the number of immature neurons and increased the number of mature neurons, but no increase in the number of mature neurons was observed after fluoxetine treatment. In addition, both running and fluoxetine reversed the decrease in the number of MAP2+ dendrites in depressed mice. Exercise increased the number of spinophilin-positive (Sp+) dendritic spines in the hippocampal CA1, CA3, and dentate gyrus (DG) regions, whereas fluoxetine only increased the number of SP+ spines in the DG. In summary, exercise promoted newborn neuron maturation in the DG and regulated neuronal plasticity in three hippocampal subregions, which might explain why running exerts earlier and more comprehensive antidepressant effects than fluoxetine.

PD48-01 SAFETY AND EFFICACY OF FLUOXETINE, SELECTIVE SEROTONIN REUPTAKE INHIBITOR, FOR THE TREATMENT OF REFRACTORY PRIMARY MONOSYMPTOMATIC NOCTURNAL ENURESIS IN CHILDREN: A RANDOMIZED PLACEBO-CONTROLLED STUDY

You have accessJournal of UrologyCME1 May 2022PD48-01 SAFETY AND EFFICACY OF FLUOXETINE, SELECTIVE SEROTONIN REUPTAKE INHIBITOR, FOR THE TREATMENT OF REFRACTORY PRIMARY MONOSYMPTOMATIC NOCTURNAL ENURESIS IN CHILDREN: A RANDOMIZED PLACEBO-CONTROLLED STUDY Mohamed Hussiny, Ahmed Abdelhalim, Abdelwahab Hashem, Mohamed A. Soltan, Mahmoud R. El-Kenawy, and Tamer Helmy Mohamed HussinyMohamed Hussiny More articles by this author , Ahmed AbdelhalimAhmed Abdelhalim More articles by this author , Abdelwahab HashemAbdelwahab Hashem More articles by this author , Mohamed A. SoltanMohamed A. Soltan More articles by this author , Mahmoud R. El-KenawyMahmoud R. El-Kenawy More articles by this author , and Tamer HelmyTamer Helmy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002616.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nocturnal Enuresis (NE) is a common medical condition in children. It affects millions of children throughout the world and is associated with a significant negative impact on self-esteem and health-related Quality of life. Behavioral therapy, alarm treatment and desmopressin are first-line treatments. Treatment options for refractory NE are limited. This study aimed at investigating the efficacy and safety of fluoxetine for treatment of refractory primary monosymptomatic NE in children. METHODS: Children aged 8-18 years with primary monosymptomatic NE refractory to desmopressin treatment were screened for eligibility. Patients with daytime symptoms, constipation, underlying urologic, neurological, endocrinological, cardiac or psychiatric conditions were excluded. After sample size calculation, patients were randomly assigned to the fluoxetine (study) or placebo groups in a 1:1 ratio. Patients in the study group were maintained on 10 mg of fluoxetine once daily for 12 weeks. The primary study outcome was reduction in the number of wet nights at 4, 8 and 12 weeks of therapy. Patients with <50% reduction of wet nights were considered non-responders. Patients with 50-99% reduction of wet nights were considered partial responders (PR) and those with complete nighttime dryness were considered complete responders (CR). Treatment adverse effects were secondary outcomes. RESULTS: Between July 2020 and March 2021, a total of 120 children with a mean age of 11.8 +2.46 years were enrolled. Those who continued the follow up duration were 110 patients. a total of 56 children were assigned to the fluoxetine and 54 to the placebo groups. Baseline enuresis severity was similar between both study groups. After 4 weeks of therapy, 7.1% of fluoxetine group achieved CR and 66.1% achieved PR (versus 0% and 16.7% of placebo, respectively; p <0.001). The response rate declined at 12 weeks of therapy with CR achieved in 10.7% and PR in 21.4% of the fluoxetine group (versus 0% and 14.8% of the placebo, respectively; p=0.023). Fluoxetine treatment was discontinued before the planned study duration in 4 patients of the fluoxetine group due to treatment-related adverse effects (dizziness in two patients, mood changes in one and hypersensitivity in another). CONCLUSIONS: Fluoxetine achieves good initial response in patients with primary refractory monosymptomatic nocturnal enuresis. However, the response rate declines significantly at 12 weeks of therapy. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e799 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Hussiny More articles by this author Ahmed Abdelhalim More articles by this author Abdelwahab Hashem More articles by this author Mohamed A. Soltan More articles by this author Mahmoud R. El-Kenawy More articles by this author Tamer Helmy More articles by this author Expand All Advertisement PDF DownloadLoading ...

Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation.

BACKGROUNDFluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.AIMTo evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.METHODSMale albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.RESULTSFluoxetine-treated rats showed elevated levels of the serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. Biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.CONCLUSIONThese findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.

Fluoxetine attenuates apoptosis in early brain injury after subarachnoid hemorrhage through Notch1/ASK1/p38 MAPK signaling pathway

ABSTRACT Subarachnoid hemorrhage (SAH) is a severe brain condition associated with a significantly high incidence and mortality. As a consequence of SAH, early brain injury (EBI) may contribute to poor SAH patient outcomes. Apoptosis is a signaling pathway contributing to post-SAH early brain injury and the diagnosis of the disease. Fluoxetine is a well-studied serotonin selective reuptake inhibitor (SSRI). However, its role in apoptosis has not been clearly understood. The present investigation assessed the effects of Fluoxetine in apoptosis and the potential Notch1/ASK1/p38 MAPK signaling pathway in EBI after SAH. Adult C57BL/6 J mice were subjected to SAH. Study mice (56) were randomly divided into 4 groups: the surgery without SAH (sham (n = 8), SAH+ vehicle; (SAH+V) (n = 16), surgery+ Fluoxetine (Fluox), (n = 16) and SAH+ Fluoxetine (n = 16). Various parameters were investigated 12, 24, 48, and 72 h after induction of SAH. Western blot analysis, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, Immunohistochemistry (IHC), and flow cytometry were carried out in every experimental group. According to the findings, the SAH downregulated NOTCH1 signaling pathway, Jlk6 inhibited Notch1, Notch1 inactivation increased apoptotic protein expression and suppressed Bax, and cytochrome C. Fluoxetine reversed the effects of notch1 inhibition in SAH. The Neuroprotective Fluoxetine effects involved suppression of apoptosis post-SAH. In summary, early Fluoxetine treatment significantly attenuates apoptosis and the expression of apoptosis-related proteins after 72 h post-SAH. Fluoxetine may ameliorate early brain injury after subarachnoid hemorrhage through anti-apoptotic effects and Notch1/ASK1/p38 MAPK signaling pathway.

Therapeutic efficacy of adipose-derived mesenchymal stem cells after chronic fluoxetine treatment on pars distalis in adult male albino rats

BackgroundFluoxetine hydrochloride is one of the most commonly used antidepressants in the selective serotonin reuptake inhibitor class. The aim of work: The study was conducted to detect the effect of chronic fluoxetine treatment on pars distalis and the possible therapeutic effect of adipose-derived mesenchymal stem cells (ADSCs). Material and methodThirty healthy male adult albino rats were classified into four groups. Control group (Group I) included fifteen rats. Fluoxetine treated (Group II) included five rats that received 24 mg/kg/day of fluoxetine dissolved in 1.0 ml of tap water once a day for 30 days. Fluoxetine group treated with ADSCs (Group III) included five rats that received fluoxetine as group (II) for 30 days, then supplied once by ADSCs at a dose of 1 × 106 cells/rat in the tail vein suspended in 0.5 ml of phosphate-buffered saline (PBS). Recovery group (Group IV) included five rats that received fluoxetine as the group (II) then received no treatment till the end of the experiment. Samples from pars distalis were processed for light, electron microscopic examination, morphometrical and statistical analyses. ResultsIn the fluoxetine-treated group, there was a disruption in cellular architecture, size, shape, and staining characteristics of pars distalis cells. The administration of ADSCs significantly improved the microscopic appearance of cells, while the recovery group showed some histological changes similar to the fluoxetine group. ConclusionFluoxetine induced various deleterious changes in the pars distalis of albino rats. These changes were almost corrected by the ADSCs treatment.

Sex and social status modify the effects of fluoxetine on socioemotional behaviors in Syrian hamsters and rhesus macaques

Social subordination increases risk for psychiatric disorders, while dominance increases resilience to these disorders. Fluoxetine, a selective serotonin (5HT) reuptake inhibitor whose actions are mediated in part by the 5HT1A receptor (5HT1AR), has sex- and social status-specific effects on socioemotional behavior and aggressive behavior. However, the impact of social status on these sex-specific effects remains unclear. The current study evaluated the impact of acute fluoxetine treatment and social status on dominance-related behaviors in female and male hamsters, and the impact of chronic fluoxetine treatment on socioemotional behavior and 5HT1AR binding potential (5HT1ARBP) in female rhesus macaques. We hypothesized that sex differences in the effects of fluoxetine on aggression in hamsters would be diminished in dominant and enhanced in subordinate males and that aggression in female hamsters would be enhanced in dominants and diminished in subordinates. In female rhesus macaques, we hypothesized that chronic fluoxetine would alter socioemotional behaviors and site-specific 5HT1ARBP in a status-dependent manner. Male (n = 46) and female (n = 56) hamsters were paired with conspecifics for three days to establish social rank. Hamsters received a single dose of 20 mg/kg fluoxetine or vehicle two-hours prior to a test with a non-aggressive intruder. Female rhesus monkeys (n = 14) housed were administered fluoxetine (2.8 mg/kg/day) or vehicle injections chronically for 14-days, separated by a three-week washout period. On Day 15, positron emission tomography neuroimaging for 5HT1ARBP was conducted. Fluoxetine treatment decreased aggression in subordinate female monkeys and subordinate female hamsters but not in dominant females of either species. Fluoxetine decreased aggression in dominant but not in subordinate male hamsters. Fluoxetine also reduced and increased prefrontal 5HT1ARBP in dominant and subordinate females, respectively. Taken together, these results provide cross-species evidence that social status and sex impact how increased 5HT modulates agonistic behavior.

Lower antidepressant response to fluoxetine is associated with anxiety-like behavior, hippocampal oxidative imbalance, and increase on peripheral IL-17 and IFN-γ levels

Major depression is a leading contributor to the global burden of disease. This is mainly related to the disorder chronic and recurrent nature, and to high rates of refractoriness to treatment. Limited efficacy with currently available antidepressants highlights the need for more effective options for treating drug-resistant patients and emphasizes the importance of developing specific preclinical models for treatment-resistant populations. Treatment-resistant depression (TRD) is commonly defined as failure to respond to two or more trials of antidepressants. In this study, we investigated the effect of fluoxetine treatment for fourteen days on the depressive-like behavior and the oxidative and inflammatory parameters of mice submitted to chronic corticosterone administration. After 21 days of subcutaneous corticosterone administration (20 mg/kg/day) and 14 days of oral fluoxetine treatment (10 mg/kg/day, started on day 7 of induction protocol), we separated animals into two groups according to the tail suspension test (TST) results: antidepressant responders (good response to antidepressant, GRA) and non-responders (resistance to antidepressant, AR). Forced swimming test (FST), elevated plus maze test (EPMT), and open field test (OFT) were performed. We found that animals classified as AR (i.e., those with higher immobility values in the TST) demonstrated anxiety-like behavior in the EPMT, increased H2O2 levels, and decreased catalase activity in the hippocampus, as well as increased serum levels of IL-17 and IFN-γ. Our findings suggest that a redox imbalance in the hippocampus, combined with increased levels of peripheral IL-17 and INF-γ, may be involved with an impaired response to fluoxetine.

Impact of Fluoxetine Treatment and Folic Acid Supplementation on the Mammary Gland Transcriptome During Peak Lactation.

Serotonin is a key regulator of mammary gland homeostasis during lactation. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat peripartum depression, but also modulates mammary gland serotonin concentrations and signaling in part through DNA methylation. The objective of this study was to determine mouse mammary transcriptome changes in response to the SSRI fluoxetine and how methyl donor supplementation, achieved by folic acid supplementation, affected the transcriptome. Female C57BL/6J mice were fed either breeder diet (containing 4 mg/kg folic acid) or supplemented diet (containing 24 mg/kg folic acid) beginning 2 weeks prior to mating, then on embryonic day 13 mice were injected daily with either saline or 20 mg/kg fluoxetine. Mammary glands were harvested at peak lactation, lactation day 10, for transcriptomic analysis. Fluoxetine but not folic acid altered circulating serotonin and calcium concentrations, and folic acid reduced mammary serotonin concentrations, however only fluoxetine altered genes in the mammary transcriptome. Fluoxetine treatment altered fifty-six genes. Elovl6 was the most significantly altered gene by fluoxetine treatment along with gene pathways involving fatty acid homeostasis, PPARγ, and adipogenesis, which are critical for milk fat synthesis. Enriched pathways in the mammary gland by fluoxetine revealed pathways including calcium signaling, serotonin receptors, milk proteins, and cellular response to cytokine stimulus which are important for lactation. Although folic acid did not impact specific genes, a less stringent pathway analysis revealed more diffuse effects where folic acid enriched pathways involving negative regulation of gene expression as expected, but additionally enriched pathways involving serotonin, glycolysis, and lactalbumin which are critical for lactation. In conclusion, peripartal SSRI use and folic acid supplementation altered critical genes related to milk synthesis and mammary gland function that are important to a successful lactation. However, folic acid supplementation did not reverse changes in the mammary gland transcriptome altered by peripartal SSRI treatment.

Oral fluoxetine treatment changes serotonergic sympatho-regulation in experimental type 1 diabetes

AimsThis study investigated whether fluoxetine treatment changes the 5-HT regulation on vascular sympathetic neurotransmission in type 1 diabetes. Main methodsFour-week diabetes was obtained by a single alloxan s.c. administration in male Wistar rats, administering fluoxetine for 14 days (10 mg/kg/day; p.o.). Systolic blood pressure, heart rate, glycaemia, body weight (BW) evolution, creatinine, and blood urea nitrogen (BUN) were monitored. Afterward, rats were pithed to perform the vascular sympathetic stimulation. 5-HT1A/1D/2A receptors expression was analysed by Western blot in thoracic aorta. Both i.v. norepinephrine and the electrical stimulation of the spinal sympathetic drive evoked vasoconstrictor responses. Key findingsFluoxetine treatment significantly reduced the BW gain, hyperglycaemia, creatinine, and BUN in diabetic rats. The electrical-produced vasopressor responses were greater in untreated than in fluoxetine-treated diabetic rats. 5-HT decreased the sympathetic-produced vasopressor responses. While 5-CT, 8-OH-DPAT and L-694,247 (5-HT1/7, 5-HT1A and 5-HT1D agonists, respectively) reproduced 5-HT-evoked inhibition, the 5-HT2 activation by α-methyl-5-HT augmented the vasoconstrictions. The 5-CT sympatho-inhibition was reversed by 5-HT1A plus 5-HT1D antagonists (WAY-100,635 and LY310762, respectively), whereas ritanserin (5-HT2A antagonist) blocked the α-methyl-5-HT potentiating effect. Norepinephrine-generated vasoconstrictions were increased or diminished by α-methyl-5-HT or 5-CT, respectively. 5-HT1A/1D/2A receptors were expressed at vascular level, being 5-HT1A expression increased by fluoxetine in diabetic rats. SignificanceOur findings suggest that fluoxetine improves metabolic and renal profiles, changes the vasopressor responses, and 5-HT receptors modulating sympathetic activity in diabetic rats: 5-HT1A/1D are involved in the sympatho-inhibition, while 5-HT2A is implicated in the sympatho-potentiation, being both effects pre and/or postjunctional in nature.

Fluoxetine ameliorates Alzheimer’s disease progression and prevents the exacerbation of cardiovascular dysfunction of socially isolated depressed rats through activation of Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathway

Depression is a risk factor for Alzheimer’s (AD) and cardiovascular diseases (CVD). Therefore, depression treatment restricts its deteriorating effects on mood, memory and CV system. Fluoxetine is the most widely used antidepressant drug, it has neuroprotective effect through its antioxidant/anti-inflammatory properties. The current study investigated for the first-time the cross link between depression, AD and CVD besides, role of fluoxetine in mitigating such disorders. Depression was induced in rats by social isolation (SI) for 12 weeks, AlCL3 (70 mg/kg/day, i.p.) was used to induce AD which was administered either in SI or normal control (NC) grouped rats starting at 8th week till the end of the experiment, fluoxetine (10 mg/kg/day, p.o) treatment also was started at 8th week. SI and AD showed a statistically significant deteriorated effect on behavioral, neurochemical and histopathological analysis which was exaggerated when two disorder combined than each alone. Fluoxetine treatment showed protective effect against SI, AD and prevents exacerbation of CVD. Fluoxetine improved animals’ behavior, increased brain monoamines, BDNF besides increased antioxidant defense mechanism of SOD, TAC contents and increased protein expression of Nrf2/HO-1 with significant decrease of AChE activity, β-amyloid, Tau protein, MDA, TNF-α, IL1β contents as well as decreased protein expression of NF-kB, TLR4, NLRP3 and caspase1. It also showed cardioprotective effects as it improved lipid profile with pronounced decrease of cardiac enzymes of CK-MB, troponin and MEF2. In conclusion, fluoxetine represents as a promising drug against central and peripheral disorders through its anti-inflammatory/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.

Fluoxetine regulates the neuronal differentiation of neural stem cells transplanted into rat brains after stroke by increasing the 5HT level

Fluoxetine, a 5-HT uptake inhibitor, has been adopted for the treatment of post-stroke depression in recent years. It has been confirmed to induce neuronal regeneration in vivo, but its effect on inducing stem cell differentiation after transplantation has not yet been verified. To evaluate its regulatory effect on stem cell differentiation, fluoxetine was used in this study to treat rats with cerebral ischemia after neural stem cell (NSC) transplantation. The results showed that the proportion of NSCs differentiating into neurons significantly increased after fluoxetine treatment. In NSC adherent culture, the addition of 5-HT but not of fluoxetine significantly increased the neuronal differentiation ratio of NSCs. Moreover, the addition of 5-HT2A or 5-HT3A antagonists inhibited this effect. In addition, Western blotting revealed that the increase in 5-HT inhibited ERK2 phosphorylation and upregulated neurogenin1 expression. In conclusion, fluoxetine increased the 5-HT level and promoted neuronal differentiation, thereby upregulating neurogenin1 expression and downregulating ERK2 phosphorylation.

Treatment of slow-channel congenital myasthenic syndrome in a Thai family with fluoxetine

The slow-channel congenital myasthenic syndrome is an autosomal dominant neuromuscular disorder caused by mutations in different subunits of the acetylcholine receptor. Fluoxetine, a common antidepressant and long-lived open-channel blocker of acetylcholine receptor, has been reported to be beneficial in the slow-channel congenital myasthenic syndrome. Here we report a prospective open label study of fluoxetine treatment in some affected members of a Thai family with slow-channel congenital myasthenic syndrome caused by a novel p.Gly153Ala (c.518G > C) mutation in CHRNA1 in the AChR α subunit. These patients showed significant clinical improvement following fluoxetine treatment but their respiratory function responded variably.

Combined Methylphenidate and Fluoxetine Treatment in Adolescent Rats Impairs Weight Gain and Skeletal Development

Combined Methylphenidate and Fluoxetine Treatment in Adolescent Rats Impairs Weight Gain and Skeletal Development

Evaluation of the antidepressant-like activity of the aqueous extract of Crataegus aronia

Background: Crataegus aronia L. Syn: Azarolus (C. aronia) is a hawthorn species and a perennial bush native to Mediterranean regions. It is recognized for its high polyphenol content and potent antioxidant effects. Research was conducted to test the antidepressant activities of an aqueous extract of C. aronia in a chronic, unpredictable, mild stress-induced rat model. Materials and Methods: Thirty-two adult Wistar male rats were divided into four groups: A control group (no stress and no treatment), stress-model group (stress and no treatment), fluoxetine-treated stress group (stress and fluoxetine treatment), and C. aronia-treated stress group (stress and C. aronia treatment). Urine samples were collected at 0, 21, 36, and 51 days. Enzyme-linked immunosorbent assay kits were used to assess serotonin, norepinephrine (NE), and dopamine (DA) levels. Results: There was a decrease in serotonin levels 3 weeks after stress exposure, but urinary NE and DA levels increased. C. aronia significantly (P < 0.001) reversed the depressive-like symptoms in the rats according to the increased urinary levels of serotonin. Moreover, C. aronia also reduced urinary levels of urinary NE and DA. The neuromodulatory effects of C. aronia were comparable to that of fluoxetine. Conclusion: With its active ingredients of anthocyanins and procyanidins, C. aronia exhibits significant antidepressant-like activity in validated stressed rats, which may be related to its neuromodulatory effects on central monoamines.

Therapeutic effect of Thymoquinone on behavioural response to UCMS and neuroinflammation in hippocampus and amygdala in BALB/c mice model.

Major depressive disorder is the leading cause of disability worldwide. The corticolimbic system plays a critical role in the emotional and cognitive aspects of major depressive disorder. Owing to the unsatisfactory efficacy of conventional antidepressants, there is a need to explore novel therapies. The current study aimed to explore the antidepressant potential of thymoquinone, a natural compound with anti-inflammatory activity, and propose its underlying mechanism of action in the unpredictable chronic mild stress (UCMS) mouse model. Coat state, forced swim test, elevated plus maze test, novelty suppressed feeding test and social interaction test were performed to quantify the behavioural shift induced by UCMS and the effect of thymoquinone and fluoxetine treatment. In addition, messenger RNA (mRNA) expression levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and BDNF and NeuN were analysed by a quantitative real-time polymerase chain reaction in the hippocampus and amygdala of experimental and control groups. UCMS significantly deteriorated coat state. Thymoquinone reinstated the resignation behaviour and latency to feed affected by UCMS. UCMS induced an increase in inflammatory cytokines (IL-1β, IL-6 and TNF-α) in the hippocampus and amygdala, which was decreased by thymoquinone. UCMS caused an increase in BDNF and NeuN mRNA levels in the amygdala while a decrease in the hippocampus. This opposite effect on BDNF was also compensated by thymoquinone; however, thymoquinone did not significantly change Ki67 and NeuN mRNA levels in the hippocampus. Thymoquinone restored the behavioural changes induced by UCMS. In addition, the antidepressant effect of thymoquinone is in line with changes in inflammatory parameters and changes in BDNF in the hippocampus and amygdala.

Design, development, and evaluation of polymer-coated delayed-release dosage form of Duloxetine hydrochloride

Medication are vital for life many medications, as tablets, suspensions, and capsules, are taken by the oral route, which has a systematic effect as it reaches different body sections via the bloodstream. Suspension is the best formulation for the treatment of various diseases such as depression for better patient compliance. Many types of drugs are there on the market for the treatment of depression-like fluoxetine, atypical antipsychotic, norepinephrine, monoamine oxidase inhibitors, a potent inhibitor of cytochrome P-450 isoenzymes, and serotonin reuptake inhibitors are also used. There are some drawbacks such as dry mouth, constipation, sedation, insomnia, tachycardia, sweating, less patient compliance, etc. Duloxetine HCl is a BCS class 2 drug that is selective serotonin and norepinephrine inhibitor. It helps to stop the pain signals in the brain by maintaining the normal levels of serotonin and norepinephrine in the brain. To overcome the drawback of patient compliance, the present study is to develop and optimize polymer-coated delayed-release suspension of Duloxetine HCl and opens a new window for researchers to develop a suspension for the treatment of depression.

Different subjective experiences of the environment are associated to different fluoxetine treatment outcomes

Different subjective experiences of the environment are associated to different fluoxetine treatment outcomes

Analysis of Adherence to Fluoxetine Treatment through its Plasma Concentration

Analysis of Adherence to Fluoxetine Treatment through its Plasma Concentration

Chronic Antidepressant Use

Background: Chronic use of antidepressant drugs often results in drug-induced organ damage, which is mostly undetected and under-reported. The study aimed at evaluating the effect of selected antidepressants on organs and blood cell counts in adult albino rats. Materials and Methods: Adult rats were divided into four groups (n = 5): Group 1 (5 mL/kg of body weight/day normal saline), Group 2 (1 mg/kg of body weight/day risperidone), Group 3 (5 mg/kg of body weight/day fluoxetine), and Group 4 (15 mg/kg of body weight/day imipramine) for 14 days. The animals experienced different stressors during the treatment period to simulate physiological state of depression. On the 14th day, the animals were exposed to the forced swimming test 1 h after the respective treatments. On the 15th day, the animals were sacrificed under halothane anesthesia. Blood sample was collected. Liver and kidney were excised for histological examination. Results were analyzed using one-way analysis of variance. Results: Kidney histology was normal for all groups. Risperidone-exposed rats presented with hepatotoxicity with areas of zonal necrosis and partial central vein congestion. Neutrophil (%) was significantly reduced (P &lt; 0.01) in all treatment groups when compared with controls. White blood cell count was significantly increased (P &lt; 0.01) in the imipramine and risperidone treatment groups but significantly reduced (P &lt; 0.01) in the fluoxetine treatment group when compared with controls. Also, the platelet count was significantly increased (P &lt; 0.01) in the fluoxetine group but decreased in imipramine-and risperidone-treated groups. Conclusion: Chronic antidepressant use can cause changes in blood cell counts and drug-induced organ damage; hence, frequent organ function tests and blood count are required in patients undergoing chronic antidepressant therapy.

Reaction of the Liver upon Long-Term Treatment of Fluoxetine and Atorvastatin Compared with Alcohol in a Mouse Model.

Background Alcoholism is known to cause liver toxicity and is extensively researched. On the other hand, stress, depression, and obesity are interrelated conditions with alcoholism, and their medications would affect the liver itself. In this study, we investigated the effects of the drugs fluoxetine and atorvastatin on the liver and compared with those of alcohol in a mouse model. Methods Comparisons of animals treated with the three drugs were carried out: serum aspartate transaminase (AST), alanine transaminase (ALT), and albumin were measured; liver tumor necrosis factor alpha (TNF alpha) and transforming growth factor beta (TGF beta-1) levels were evaluated; proliferative cells were detected via immunohistochemistry (IHC) targeting on proliferating cell nuclear antigen (PCNA) and minichromosome maintenance complex component 2 (MCM2); for apoptosis, IHC targeting on activated caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were employed; and histopathology was also documented in all groups. Results For ALT, AST, albumin, and liver TNF alpha, only the ethanol group surged to significantly higher levels. For TGF beta-1, both ethanol and atorvastatin groups reached a significantly higher level. PCNA and MCM2 showed increased proliferation in the livers of all three groups, with the ethanol group having the highest number of positive cells followed by atorvastatin and then the fluoxetine group. As for cell death, both ethanol and fluoxetine groups showed significantly more apoptosis than control in TUNEL and activated caspase-3, while in the atorvastatin group, activated caspase-3 positive cells increased significantly, but the increase in TUNEL-positive cells did not reach statistical significance.