Search results for: Serotonin

Authors: Mazin Alqhazo, Ayat Bani Rashaid

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This study examines the levels of dopamine and serotonin in blood samples of children who stutter compared with normal fluent speakers. Blood specimens from 50 children who stutter (6 females, 44 males) and 50 normal children matched age and gender were collected for the purpose of the current study. The concentrations of dopamine and serotonin were measured using the 1100 series high-performance liquid chromatography coupled with ultraviolet detector instrument (HPLC-UV). It was revealed that dopamine level in the blood samples of stuttering group and fluent group was not significant (P = 0.769), whereas the level of serotonin was significantly higher in the blood samples of stuttering group than the blood samples of fluent normal group (P = 0.015). It is concluded that serotonin blockers could be used in future studies to evaluate its role as a medication for the treatment of stuttering.

Keywords: dopamine, serotonin, stuttering, fluent speakers

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Authors: Arunima Verma, Padmabati Mondal

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Serotonin-receptor binding plays a key role in several neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. In this article, we performed molecular dynamics simulation to examine the key residues that play an essential role in the binding of serotonin to the G-protein-coupled 5-HT₁ᴮ receptor (5-HT₁ᴮ R) via electrostatic interactions. An end-point free energy calculation method (MM-PBSA) determines the stability of the 5-HT1B R due to serotonin binding. The single-point mutation of the polar or charged amino acid residues (Asp129, Thr134) on the binding sites and the calculation of binding free energy validate the importance of these residues in the stability of the serotonin-receptor complex. Principal component analysis indicates the serotonin-bound 5-HT1BR is more stabilized than the apo-receptor in terms of dynamical changes. The difference dynamic cross-correlations map shows the correlation between the transmembrane and mini-Go, which indicates signal transduction happening between mini-Go and the receptor. Allosteric communication reveals the key nodes for signal transduction in 5-HT1BR. These results provide useful insights into the signal transduction pathways and mutagenesis study to regulate the functionality of the complex. The developed protocols can be applied to study local non-covalent interactions and long-range allosteric communications in any protein-ligand system for computer-aided drug design.

Keywords: allostery, CADD, MD simulations, MM-PBSA

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Authors: Sunil Kumar, Uday C. Ghoshal

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Background and aims: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhea predominant IBS (D-IBS) phenotype Subjects: A total of 36 northern Indian female patients and 55 female northern Indian healthy controls (HC) were subjected to genotyping. Methods: Leucocyte DNA of all subjects was analyzed by polymerase chain reaction based technologies for SERT polymorphisms, specifically the insertion/deletion polymorphism in the promoter (SERT-P). Statistical analysis was performed to assess association of SERT polymorphism allele with the D-IBS phenotype. Results: The frequency of distribution of SERT-P gene was comparable between female patients with IBS and HC (p = 0.086). However, frequency of SERT-P deletion/deletion genotype was significantly higher in female patients with D-IBS compared to C-IBS and A-IBS [17/19 (89.5%) vs. 4/12 (33.3%) vs. 1/5 (20%), p=0.001, respectively]. The mucosal level of serotonin was higher in D-IBS compared to C-IBS and A-IBS [Median, range (159.26, 98.78–212.1) vs. 110.4, 67.87–143.53 vs. 92.34, 78.8–166.3 pmol/mL, p=0.001, respectively]. The mucosal level of serotonin was higher in female patients with IBS with SERT-P deletion/deletion genotype compared deletion/insertion and insertion/insertion [157.65, 67.87–212.1 vs. 110.4, 78.1–143.32 vs. 100.5, 69.1–132.03 pmol/mL, p=0.001, respectively]. Patients with D-IBS with deletion/deletion genotype more often reported symptoms of abdominal pain, discomfort (p=0.025) and bloating (p=0.039). Symptoms development following lactose ingestion was strongly associated with D-IBS and SERT-P deletion/deletion genotype (p=0.004). Conclusions: Significant association was observed between D-IBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for D-IBS in women.

Keywords: serotonin, SERT, inflammatory bowel disease, genetic polymorphism

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Authors: Hee Soo Kim, Ha Young Kyung

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Happiness and pleasure are a result of dopamine, oxytocin, serotonin, and endorphin levels in the body. In order to increase the four neurochemical levels, it is important to associate daily activities with its corresponding neurochemical releases. This includes setting goals, maintaining social relationships, laughing frequently, and exercising regularly. The likelihood of experiencing happiness increases when all four neurochemicals are released at the optimal level. The achievement of happiness is important because it increases healthiness, productivity, and the ability to overcome adversity. To process emotions, electrical brain waves, brain structure, and neurochemicals must be analyzed. This research uses Chemcraft and Avogadro to determine the theoretical and chemical properties of the four neurochemical molecules. Each neurochemical molecule’s thermodynamic stability is calculated to observe the efficiency of the molecules. The study found that among dopamine, oxytocin, serotonin, alpha-, beta-, and gamma-endorphin, beta-endorphin has the lowest optimized energy of 388.510 kJ/mol. Beta-endorphin, a neurotransmitter involved in mitigating pain and stress, is the most thermodynamically stable and efficient molecule that is involved in the process of happiness. Through examining such properties of happiness neurotransmitters, the science of happiness is better understood.

Keywords: happiness, neurotransmitters, positive psychology, dopamine, oxytocin, serotonin, endorphins

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Authors: G. A. Ravishankar, A. Ramakrishna

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Melatonin (MEL) and Serotonin (SER), also known as [5-Hydroxytryptamine (5-HT)] are reported to be in a range of plant types which are edible. Their occurrence in plants species appears to be ubiquitous. Their presence in high quantities in plants assumes significance owing to their physiological effects upon consumption by human beings. MEL is a well known animal hormone mainly released by the pineal gland known to influence circadian rhythm, sleep, apart from immune enhancement. Similarly, SER is a neurotransmitter that regulates mood, sleep and anxiety in mammals. It is implicated in memory, behavioral changes, scavenging reactive oxygen species, antipsychotic, etc. Similarly Role of SER and MEL in plant morphogenesis, and various physiological processes through intense research is beginning to unfold. These molecules are in common foods viz banana, pineapple, plum, nuts, milk, grape wine. N- Feruloyl serotonin and p-coumaroyl serotonin found in certain seeds are found to possess antioxidant, anti-inflammatory, antitumor, antibacterial, and anti-stress potential apart from reducing depression and anxiety. MEL is found in Mediterranean diets, nuts, cherries, tomato berries, and olive products. Consumption of foods rich in MEL is known to increase blood MEL levels which have been implicated in protective effect against cardiovascular damage, cancer initiation and growth. MEL is also found in wines, green tea, beer, olive oil etc. Moreover, presence of SER and MEL in Coffee beans (green and roasted beans) and decoction has been reported us. In this communication we report the occurrence of indole amines in edible plants and their implications in human health.

Keywords: serotonin, melatonin, edible plants, neurotransmitters, physiological effects

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Authors: Suliman Khan, Rabeea Siddique, Mengzhou Xue

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Background: Patients with neurological disorders often display altered circadian rhythms. The disrupted circadian rhythms through chronic jetlag or shiftwork are thought to increase the risk and severity of human disease, including cancer, psychiatric, and related brain diseases. In this study, we investigated the impact of shiftwork or chronic jetlag (CJL) like conditions on mice’s brains. Transcriptome profiling based on RNA sequencing revealed that genes associated with serious neurological disorders were differentially expressed in the nucleus accumbens (NAc) and prefrontal cortex (PFC). According to the qPCR analysis, several key regulatory genes associated with neurological disorders were significantly altered in the NAc, PFC, hypothalamus, hippocampus, and striatum. Serotonin levels and the expression levels of serotonin transporters and receptors were significantly altered in mice treated with CJL. Overall, these results indicate that CJL may increase the risk of neurological disorders by disrupting the key regulatory genes, biological functions, serotonin, and corticosterone. These molecular linkages can further be studied to investigate the mechanism underlying CJL or shiftwork-mediated neurological disorders in order to develop treatment strategies.

Keywords: chronic jetlag, molecular profiles, brain disorders, circadian rhythms

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Authors: Aizati N. A. Daud, Jorieke E. H. Bergman, Wilhelmina S. Kerstjens-Frederikse, Pieter Van Der Vlies, Eelko Hak, Rolf M. F. Berger, Henk Groen, Bob Wilffert

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Prenatal use of SRIs was previously associated with Congenital Heart Anomalies (CHA). The aim of the study is to explore whether pharmacogenetics plays a role in this teratogenicity using a gene-environment interaction study. A total of 33 case-mother dyads and 2 mother-only (children deceased) registered in EUROCAT Northern Netherlands were included in a case-only study. Five case-mother dyads and two mothers-only were exposed to SRIs (paroxetine=3, fluoxetine=2, venlafaxine=1, paroxetine and venlafaxine=1) in the first trimester of pregnancy. The remaining 28 case-mother dyads were not exposed to SRIs. Ten genes that encode the enzymes or proteins important in determining fetal exposure to SRIs or its mechanism of action were selected: CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6), ABCB1 (placental P-glycoprotein), SLC6A4 (serotonin transporter) and serotonin receptor genes (HTR1A, HTR1B, HTR2A, and HTR3B). All included subjects were genotyped for 58 genetic variations in these ten genes. Logistic regression analyses were performed to determine the interaction odds ratio (OR) between genetic variations and SRIs exposure on the risk of CHA. Due to low phenotype frequencies of CYP450 poor metabolizers among exposed cases, the OR cannot be calculated. For ABCB1, there was no indication of changes in the risk of CHA with any of the ABCB1 SNPs in the children and their mothers. Several genetic variations of the serotonin transporter and receptors (SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 & rs6298, HTR3B rs1176744) were associated with an increased risk of CHA, but with too limited sample size to reach statistical significance. For SLC6A4 genetic variations, the mean genetic scores of the exposed case-mothers tended to be higher than the unexposed mothers (2.5 ± 0.8 and 1.88 ± 0.7, respectively; p=0.061). For SNPs of the serotonin receptors, the mean genetic score for exposed cases (children) tended to be higher than the unexposed cases (3.4 ± 2.2, and 1.9 ± 1.6, respectively; p=0.065). This study might be among the first to explore the potential gene-environment interaction between pharmacogenetic determinants and SRIs use on the risk of CHA. With small sample sizes, it was not possible to find a significant interaction. However, there were indications for a role of serotonin receptor polymorphisms in fetuses exposed to SRIs on fetal risk of CHA which warrants further investigation.

Keywords: gene-environment interaction, heart defects, pharmacogenetics, serotonin reuptake inhibitors, teratogenicity

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Authors: Siriwan Nantaphol, Robert B. Channon, Takeshi Kondo, Weena Siangproh, Orawon Chailapakul, Charles S. Henry

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In this work, we demonstrate a novel electrochemically reduced graphene oxide (ERGO) modified boron-doped diamond paste (BDDP) electrode on paper-based analytical devices (PADs) for simultaneous determination of norepinephrine (NE) and serotonin (5-HT). The BDD paste electrode was easily constructed by filling BDD paste in small channels, which made in transparency film sheets using a CO₂ laser etching 
system. The counter and reference electrodes were fabricated on paper by in-house screen-printing and then combined with BDD paste microelectrode. The electrochemical characterization of the device was investigated by cyclic voltammetry (CV). Differential pulse voltammetry (DPV) was employed for the simultaneous determination of NE and 5-HT. The ERGO-modified BDDP electrode displayed excellent electrocatalytic activities toward the oxidation of NE and 5-HT and strong function for resolving the overlapping voltammetric responses of NE and 5-HT into two well-defined voltammetric peaks. This device was capable of simultaneously detecting NE and 5-HT in wide concentration ranges and with a low limit of detections. In addition, it has the advantages in terms of ease of use, low cost, and disposability.

Keywords: boron-doped diamond paste electrode, electrochemically reduced graphene oxide, norepinephrine, paper-based analytical device, serotonin

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Authors: D: Gupta, M. Radhakrishnan, Y. Kurhe, D. Thangaraj

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Depression is among the leading causes of death worldwide. The current pharmacotherapy is associated with poor compliance, resistance and relapse, which necessitate the development of novel compounds with better efficacy. The present study designed and synthesized EQC-34 (N-cyclohexyl-3-ethoxyquinoxalin-2-carboxamide) as novel serotonin type-3 (5HT3) antagonist and evaluated its antidepressant-like effects using neurobehavioral mouse model. 5HT3 antagonism (as pA2 value) was determined on the longitudinal smooth muscle of guinea-pig ileum against 2-methyl-5HT (a 5HT3 agonist). The doses were calculated by dose response of basal locomotor activity. Consequently, effects of EQC-34 on neurobehavioral parameters were measured in forced swim (FST) and tail suspension test (TST). The possible mechanism was estimated by interaction study with fluoxetine (a selective serotonin reuptake inhibitor) and mCPBG (1-(m-chlorophenyl)-biguanide, a selective 5HT3 agonist), and confirmed by potentiation of head twitch response by 5hydroxy-L-tryptophan (5HTP). EQC-34 (1-4 mg/kg, i.p.) produced significant decreased behavioral despair effects in FST and TST. It potentiated fluoxetine response, while mCPBG reduced EQC-34 activity in FST. Further, EQC-34 potentiated 5HTP induced head twitch response. EQC-34 revealed potential antidepressant-like effects, which may involve 5HT3 receptor mediated facilitation of 5HT neurotransmission, thereby reversing the pathological deficiency of monoamines (5HT) observed in depression. Thus, it may be further investigated as promising agent to improve therapeutics of depression.

Keywords: depression, forced swim test, 5HT3 receptor antagonist, serotonin

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Authors: Mohaya Farzin, Shahin Hassanpour, Morteza Zendehdel, Bita Vazir, Ahmad Asghari

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Aim: There are several differences between birds and mammals in terms of food intake regulation. Therefore, this study aimed to investigate the effects of the intracerebroventricular (ICV) injection of spexin and its interaction with nitric oxide, serotonin, and corticotropin receptors on central food intake regulation in broiler chickens. Materials and Methods: In experiment 1, chickens received ICV injection of saline, PCPA (p-chlorophenyl alanine,1.25 µg), spexin, and PCPA+spexin. In experiments 2-7, 8-OH-DPAT (5-HT1A agonist, 15.25 nmol), SB-242084 (5-HT2C receptor antagonist, 1.5µg), L-arginine (Precursor of nitric oxide, 200 nmol), L-NAME (nitric oxide synthetase inhibitor, 100 nmol), Astressin-B (CRF1/CRF2 receptor antagonist, 30 µg) and Astressin2-B (CRF2 receptor antagonist, 30 µg) were injected to chickens instead of the PCPA. Then, food intake was measured until 120 minutes after the injection. Results: Spexin significantly decreased food consumption (P<0.05). Concomitant injection of SB-242084+spexin attenuated spexin-induced hypophagia (P<0.05). Co-injection of L-arginine+spexin enhanced spexin-induced hypophagia, and this effect was reversed by L-NAME (P<0.05). Also, concomitant injection of Astressin-B + spexin or Astressin2-B + spexin enhanced spexin-induced hypophagia (P<0.05). Conclusions: Based on these observations, spexin-induced hypophagia may be mediated by nitric oxide and 5-HT2C, CRF1, and CRF2 receptors in neonatal broiler chickens.

Keywords: spexin, serotonin, corticotropin, nitric oxide, food intake, chicken

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Authors: Devasis Ghosh

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The main hindrance to total cure of cancer is a) the failure to control continued production of cancer cells, b) its sustenance and c) its metastasis. This review study has tried to address this issue of total cancer cure in a more innovative way. A 10-pronged “CRAB METHOD”, a novel holistic scientific approach of Cancer treatment has been hypothesized in this paper. Apart from available Chemotherapy, Radiotherapy and Oncosurgery, (which shall not be discussed here), seven other points of interference and treatment has been suggested, i.e. 1. Efficient stress management. 2. Dampening of ATF3 expression. 3. Selective inhibition of Platelet Activity. 4. Modulation of serotonin production, metabolism and 5HT receptor antagonism. 5. Auxin, its anti-proliferative potential and its modulation. 6. Melatonin supplementation because of its oncostatic properties. 7. HDAC Inhibitors especially valproic acid use due to its apoptotic role in many cancers. If all the above stated seven steps are thoroughly taken care of at the time of initial diagnosis of cancer along with the available treatment modalities of Chemotherapy, Radiotherapy and Oncosurgery, then perhaps, the morbidity and mortality rate of cancer may be greatly reduced.

Keywords: ATF3 dampening, auxin modulation, cancer, platelet activation, serotonin, stress, valproic acid

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Authors: Sh. Khoshemehry, M. E. Bahram, M. J. Pourvaghar

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Sport has found a special place as an effective phenomenon in all societies of the contemporary world. The relationship between physical activity and exercise with different sciences has provided new fields for human study. The range of issues related to exercise and physical education is such that it requires specialized sciences and special studies. In this article, the psychological and social sections of exercise have been investigated for children and adults. It can be used for anyone in different age groups. Exercise and regular physical movements have a great impact on the mental and social health of the individual in addition to body health. It affects the individual's adaptability in society and his/her personality. Exercise affects the treatment of diseases such as depression, anxiety, stress, body image, and memory. Exercise is a safe haven for young people to achieve the optimum human development in its shelter. The effects of sensorimotor skills on mental actions and mental development are such a way that many psychologists and sports science experts believe these activities should be included in training programs in the first place. Familiarity of students and scholars with different programs and methods of sensorimotor activities not only causes their mental actions; but also increases mental health and vitality, enhances self-confidence and, therefore, mental health.

Keywords: anxiety, mental health, physical activity, serotonin

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Authors: Esra Bora, Alper Omeroglu, Zeynep Pelin Polat, Oguzhan Kara, Fatih Akdogan, Sema Ucak Basat

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Hyponatremia is one of the most encountered electrolyte imbalance among all medical fields. It has a wide range of symptoms as well as complications from fatigue to loss of consciousness. Although a lot of factors can cause low sodium levels in serum, combining specific medications can lead to severe hyponatremia in a rapid onset which can cause high mortality and morbidity. The objective of this case report was to underline that prescribing specific medications disregarding their side effects can cause this common electrolyte imbalance but in a more severe manner. In this case report, we present a 46-year-old male patient with a serum sodium level of 104 mEq/L who consumed hydrochlorothiazide for hypertension and was under treatment with selective serotonin reuptake inhibitors (SSRIs) for major depression. The patient had tonic-clonic seizures at the second hour of the treatment and intubation was needed due to loss of consciousness and hypoxia. After proper replacement of sodium with hypertonic solutions in intensive care unit for nine days, extubation indicated. Even in healthy young males, hyponatremia due to two separately prescribed medications can lead life-threatening hyponatremia. Physicians should be aware of the side effects of diuretics, especially hydrochlorothiazides and SSRIs and their combinations.

Keywords: diuretics, hydrochlorothiazide, hyponatremia, SSRI

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Authors: Liu Wei-Hsien, Chuang Hsiao-Li, Huang Yen-Te, Wu Chien-Chen, Chou Geng-Ting, Tsai Ying-Chieh

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Intestinal microflora play an important role in communication along the gut-brain axis. Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host. Here we administered Lactobacillus plantarum PS128 (PS128) to the germ-free (GF) mouse to investigate the impact of the gut-brain axis on emotional behavior. Administration of live PS128 significantly increased the total distance traveled in the open field test; it decreased the time spent in the closed arm and increased the time spent and total entries into the open arm in the elevated plus maze. In contrast, heat-killed PS128 caused no significant changes in the GF mice. Treatment with live PS128 significantly increased levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. However, live PS128 did not alter pro- or anti-inflammatory cytokine production by mitogen-stimulated splenocytes. The above data indicate that the normalization of emotional behavior correlated with monoamine neurotransmission, but not with immune activity. Our findings suggest that daily intake of the probiotic PS128 could ameliorate neuropsychiatric disorders such as anxiety and excessive psychological stress.

Keywords: dopamine, hypothalamic-pituitary-adrenal axis, intestinal microflora, serotonin

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Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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Authors: Jaspreet Kaur, Parminder Nain, Vipin Saini, Sumitra Dahiya

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Elaeocarpus sphaericus has been traditionally used in the Indian traditional medicine system for the treatment of stress, anxiety, depression, palpitation, epilepsy, migraine and lack of concentration. The study was investigated to evaluate the neurological potential such as anxiolytic, muscle relaxant and sedative activity of methanolic extract of Elaeocarpus sphaericus stem bark (MEESSB) in mice. Preliminary phytochemical screening and acute oral toxicity of MEESSB was carried out by using standard methods. The anxiety was induced by employing Elevated Plus-Maze (EPM), Light and Dark Test (LDT), Open Field Test (OFT) and Social Interaction test (SIT). The motor coordination and sedative effect was also observed by using actophotometer, rota-rod apparatus and ketamine-induced sleeping time, respectively. Animals were treated with different doses of MEESSB (i.e.100, 200, 400 and 800 mg/kg orally) and diazepam (2 mg/kg i.p) for 21 days. Brain neurotransmitters like dopamine, serotonin and nor-epinephrine level were estimated by validated methods. Preliminary phytochemical analysis of the extract revealed the presence of tannins, phytosterols, steroids and alkaloids. In the acute toxicity studies, MEESSB was found to be non-toxic and with no mortality. In anxiolytic studies, the different doses of MEESSB showed a significant (p<0.05) effect on EPM and LDT. In OFT and SIT, a significant (p<0.05) increase in ambulation, rearing and social interaction time was observed. In the case of motor coordination activity, the MEESSB does not cause any significant effect on the latency to fall off from the rotarod bar as compared to the control group. Moreover, no significant effects on ketamine-induced sleep latency and total sleeping time induced by ketamine were observed. Results of neurotransmitter estimation revealed the increased concentration of dopamine, whereas the level of serotonin and nor-epinephrine was found to be decreased in the mice brain, with MEESSB at dose 800 mg/kg only. The study has validated the folkloric use of the plant as an anxiolytic in Indian traditional medicine while also suggesting potential usefulness in the treatment of stress and anxiety without causing sedation.

Keywords: anxiolytic, behavior experiments, brain neurotransmitters, elaeocarpus sphaericus

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Authors: Donald Kushon, Jyoti Pillai

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Psychogenic Non-epileptic Seizure Disorder (PNES) is a challenging clinical problem for the neurologist. This study explores the benefits of on-site collaboration between psychiatry and neurology in the management of PNES. A 3 month period at a university hospital seizure clinic is described detailing specific management approaches taken as a result of this collaboration. This study describes four areas of interest: (1. After the video EEG results confirm the diagnosis of PNES, the presentation of the diagnosis of PNES to the patient. (2. The identification of co-morbid psychiatric illness (3. Treatment with specific psychotherapeutic interventions (including Cognitive Behavioral Therapy) and psychopharmacologic interventions (primarily SSRIs) and (4. Preliminary treatment outcomes.

Keywords: cognitive behavioral therapy (CBT), psychogenic non-epileptic seizure disorder (PNES), selective serotonin reuptake inhibitors (SSRIs), video electroencephalogram (VEEG)

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Authors: Chirag Kothawade, Gourie Jagtap, PreetKaur Relusinghani, Vedang Chavan, Smitha S. Bhosale

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Psychological research has proven that music relieves stress, elevates mood, and is responsible for the release of “feel-good” chemicals like oxytocin, serotonin, and dopamine. It comes as no surprise that music has been a popular tool in rehabilitation centers and therapy for various disorders, thus with the interminably rising numbers of people facing mental health-related issues across the globe, addressing mental health concerns is more crucial than ever. Despite the existing music recommendation systems, there is a dearth of holistically curated algorithms that take care of the needs of users. Given that, an undeniable majority of people turn to music on a regular basis and that music has been proven to increase cognition, memory, and sleep quality while reducing anxiety, pain, and blood pressure, it is the need of the hour to fashion a product that extracts all the benefits of music in the most extensive and deployable method possible. Our project aims to ameliorate our users’ mental state by building a comprehensive mood-based music recommendation system called “Viby”.

Keywords: language, communication, speech recognition, interaction

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Azadeh Moghaddas, Mehrnoush Dianatkhah, Padideh Ghaeli

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The main characteristics of borderline personality disorder (BPD) are instable regulation of affect and self-image, impulsive behavior, and lack of interpersonal relationships. Clinically, emotional dysregulation, impulsive aggression, repeated self-injury, and suicidal thought are noted with this disorder. Proper management of patients with BPD is a difficult challenge due to the complex features of this disorder. Pharmacotherapy of BPD in order to control impulsive behavior and to stabilize affect in patients with BPD has been receiving a lot of attention. Anticonvulsant agents such as topiramate, valproate, or lamotrigine, atypical antipsychotics such as aripiprazole and olanzapine and antidepressants such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors like fluvoxamine have been implicated in the treatment of BPD. Unfortunately, none of these medications can be used alone or even in combination as sole treatment of BPD. Medications may be used mostly to resolve or reduce impulsivity and aggression in these patients. Naltrexone (NTX), a nonspecific competitive opiate antagonist has been suggested, in the literature, to control self-injurious behavior (SIB) and dissociative symptoms in patients with BPD. This brief review has been intended to look at all documented evidence on the use of NTX in the management of BPD and to reach a comprehensive conclusion.

Keywords: borderline personality disorder, naltrexone, self-injurious behavior, dissociative symptoms

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Authors: E. Kuley, M. Durmuş, E. Balikci, G. Ozyurt, Y. Uçar, F. Kuley, F. Ozogul, Y. Ozogul

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Ammonia and biogenic amine production of fish spoilage bacteria in sardine infusion decarboxylase broth and antimicrobial effect of olive by products (olive leaf extract:OL, olive cake: OC and black water:BW) was monitored using HPLC method. Fish spoilage bacteria produced all biogenic amine tested, mainly histamine and serotonin. Ammonia was accumulated more than 13.60 mg/L. Histamine production was in range 37.50 mg/L by Ser. liquefaciens and 86.71 mg/L by Ent. cloacae. The highest putrescine and cadaverine production was observed by Ent. cloacae (17.80 vs. 17.69 mg/L). The presence of OL, OC and BW in the broth significantly affected biogenic amine accumulation by bacteria. The antibacterial effect of olive by products depended on bacterial strains. OL and OC resulted in significant inhibition effect on HIS accumulation by bacteria apart from Ser. liquefaciens and Prot. mirabilis. The study result revealed that usefulness of OL and OC to prevent the accumulation of this amine which may affect human health.

Keywords: Antimicrobials, biogenic amine, fish spoilage bacteria, olive-by products

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Authors: A. Bouaouiche, M. S. Boulakoud

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The functioning of the pineal gland, the transducer body of environmental information to the neuroendocrine system is subject to a circadian rhythm. Melatonin is the main neuro-hormone expressing this operation. It is synthesized in the pinealocytes after conversion serotonin via N-acetyl-transferase enzyme, itself subject to a photoperiodic modulation (activation dark inhibition by light). Some authors have suggested that melatonin is involved in diabetic disease and found that it could have a diabetogenic effect. To this study the effect of this hormone on glucose metabolism has long been subject to controversy. Agreeing in effect and hyperinsulinemic hypoglycemic effect. In order to illustrate the level of interaction of melatonin with neuro-immune- corticotropin axis and its impact on carbohydrate metabolism, we studied the impact homeostatic (glucose) through the solicitation of two control systems (gland pineal and corticotropin axis). We then found that melatonin could have an indirect influence on insulin control (glucose metabolism) to the levels of the growth hormone axis (somatostatin) and adrenocorticotropic (corticotropin). In addition, we have suggested that melatonin might limit the hyperglycemic action of corticosteroids by direct action at peripheral level.

Keywords: pinéal gland, melatonin, neuro-immuno-corticotrop, metabolism

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Authors: Rachid Mosbah, Aziez Chettoum, Zouhir Djerrou, Alberto Mantovani

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Selective serotonin reuptake inhibitors (SSRI) are a class of molecules used in treating depression, anxiety, and mood disorders. Paroxetine (PRT) is one of the mostly prescribed antidepressant which has attracted great attention regarding its side effects in recent years. This study was planned to assess the adverse effects of PRT on the biochemical parameters and reproductive system. Fourteen male Wistar rats were randomly allocated into two groups (7 rats or each): control and treated with PRT at dose of 5mg/kg.bw for two weeks. At the end of the experiment, blood was collected from retro orbital plexus for measuring the biochemical parameters, whereas the reproductive organs were removed for measuring semen quality and the histological investigations. Results showed that PRT induced significant changes in some biochemical parameters and alteration of semen quality including sperm count, spermatids number and sperm viability, motility, and abnormalities. The histopathological examinations of testis and epididymis revealed an alteration of spermatogenesis, cellular disorganization and vacuolization, enlargement of interstitial space, shrinkage and degenerative changes in the epithelium of seminiferous and epididymal tubules with few to nil numbers of spermatozoa in their lumen. In conclusion, PRT treatment caused changes in some biochemical parameters and sperm profile as well as histopathologic effects of reproductive organs.

Keywords: antidepressant, biochemical parameters, reproductive function, paroxetine

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Authors: Bilal Ahmad

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Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses. However, how Gut-microbiota plays a role in the pathogenesis of AD is not well elucidated. The purpose of this literature review is to summarize and understand the current findings that may elucidate the gut microbiota's role in the development of AD. Methods: A literature review of all the relevant papers known to the author was conducted. Relevant articles, abstracts and research papers were collected from well-accepted web sources like PubMed, PMC, and Google Scholar. Results: Recent studies have shown that Gut-microbiota has an important role in the progression of AD via Gut-Microbiota-Brain Axis. The onset of AD supports the ‘Hygiene Hypothesis’, which shows that AD might begin in the Gut, causing dysbiosis, which interferes with the intestinal barrier by releasing pro-inflammatory cytokines and making its way up to the brain via the blood-brain barrier (BBB). Molecular mechanisms lipopolysaccharides and serotonin kynurenine (tryptophan) pathways have a direct association with inflammation, the immune system, neurodegeneration, and AD. Conclusion: The studies helped to analyze the molecular basis of AD, other neurological conditions like depression, autism, and Parkinson's disease and how they are linked to Gut-microbiota. Further, studies to explore the therapeutic effects of probiotics in AD and cognitive enhancement should be warranted to provide significant clinical and practical value.

Keywords: gut-microbiota, Alzheimer’s disease, second brain aging, lipopolysaccharides, short-chain fatty acids

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Authors: Pinhas Dannon, Aviv Weinstein

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Impulsivity is raising major interest clinically because it is associated with various clinical conditions such as delinquency, antisocial behavior, suicide attempts, aggression, and criminal activity. The evolutionary perspective argued that impulsivity relates to self-regulation and it has predicted that female individuals should have evolved a greater ability to inhibit pre-potent responses. There is supportive evidence showing that female individuals have better performance on cognitive tasks measuring impulsivity such as delay in gratification and delayed discounting mainly in childhood. During adolescence, brain imaging studies using diffusion tensor imaging on white matter architecture indicated contrary to the evolutionary perspective hypothesis, that young adolescent male individuals may be less vulnerable than age-matched female individuals to risk- and reward- related maladaptive behaviors. In adults, the results are mixed presumably owing to hormonal effects on neuro-biological mechanisms of reward. Consequently, female individuals were less impulsive than male individuals only during fertile stages of the menstrual cycle. Finally, there is evidence the serotonin (5-HT) system is more involved in the impulsivity of men than in that of women. Overall, there seem to be sex differences in impulsivity but these differences are more pronounced in childhood and they are later subject to maturational and hormonal changes during adolescence and adulthood and their effects on the brain, cognition, and behavior.

Keywords: impulse control, male population, female population, gender differences, reward, neurocognitive tests

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Authors: Siamak Shahidi, Nasrin Hashemi-Firouzi, Sara Soleimani-Asl, Alireza Komaki

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Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory and cognitive performance. Recently, an involvement of the serotonergic system and their receptors are suspected in the AD progression. In the present behavioral study, the effects of BIMU (selective 5-HT4 receptor agonist) on cognition and memory in the rat model of AD was investigated. Material and Methods: The animal model of the AD was induced by intracerebroventricular (Icv) injection of amyloid beta (Aβ) in adult male Wistar rats. Animals were divided into experimental groups included control, sham, Aβ, Aβ +BIMU groups. The treatment substances were icv injected (1 μg/μL) for thirty consecutive days. Then, novel object recognition (NOR) and passive avoidance learning (PAL) tests were applied to investigate memory and cognitive performance. Results: Aβ decrease the discrimination index of NOR test. Also, it increases the time spent in the dark compartment during PAL test, as compared with sham and control groups. In addition, compared to Aβ groups, BIMU significantly increased the discrimination index of NOR test and decreased the time spent in the dark compartment of PAL test. Conclusion: These findings suggest that 5-HT4 receptor activation prevents progression of memory and cognitive impairment in a rat model of AD.

Keywords: Alzheimer disease, cognition, memory, serotonin receptors

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Authors: Fatih Özogul, Nurten Toy, Yesim Özogul

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The influences of cell-free solutions (CFSs) of lactic acid bacteria (LAB) on cadaverine and other biogenic amine production by Listeria monocytogenes and Staphylococcus aureus were investigated in lysine decarboxylase broth (LDB) using HPLC. Cell-free solutions were prepared from Lactococcus lactis subsp. lactis, Leuconostoc mesenteroides subsp. cremoris, Pediococcus acidophilus and Streptococcus thermophiles. Two different concentrations that were 50% and 25% CFS and the control without CFSs were prepared. Significant variations on biogenic amine production were observed in the presence of L. monocytogenes and S. aureus (P<0.05). The role of CFS on biogenic amine production by foodborne pathogens varied depending on strains and specific amine. Cadaverine formation in control by L. monocytogenes and S. aureus were 500.9 and 948.1 mg/L, respectively while the CFSs of LAB induced 4-fold lower cadaverine production by L. monocytogenes and 7-fold lower cadaverine production by S. aureus. CFSs resulted in strong decreases in cadaverine and putrescine production by L. monocytogenes and S. aureus, although remarkable increases were observed for histamine, spermidine, spermine, serotonin, dopamine, tyramine, and agmatine, in the presence of LAB in lysine decarboxylase broth.

Keywords: cell-free solution, lactic acid bacteria, cadaverine, food borne-pathogen

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Authors: Amir Bastani

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The result of the research in the field of human behavioural genetics demonstrates a genetic contribution of behavioural differences in aggression, violence, drug and substance abuse, antisocial personality disorder and other related traits. As the field of human behavioural genetics progresses and achieves credibility, the criminal accused continue to use its types of evidence into the criminal law. One of the most important genetic factors which controls certain neurotransmitters like dopamine and serotonin is the Monoamine Oxidase Acid A (MAOA) gene, known as the 'warrior gene'. The high-profile study by Caspi and colleagues in 2002 showed that the combination between one type of variation of the MAOA gene and childhood maltreatment noticeably predisposes a person to antisocial behaviour. Moreover, further scientific research shows that individuals with the MAOA gene have to some degree difficulties in controlling their impulses. Based on the evidence of MAOA, some criminal accused claimed difficulties in self-control. In the first case – the famous case of Mobley – the court rejected the MAOA evidence on the ground of the lack of scientific support. In contrast, in other cases after the Mobley trial, courts accepted the evidence of MAOA. In this paper, the issue of lack of impulse control produced by the MAOA gene and cases which relied on the MAOA evidence and successfully being accepted will be reviewed in detail. Finally, the anticipation of the paper for the future use of the MAOA evidence in criminal cases will be presented.

Keywords: genetic defence, criminal responsibility, MAOA, self-control

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Authors: Andreas Aceranti, Sergio Romanò, Simonetta Vernocchi, Silvia Arnaboldi, Emilio Mazza

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As a result of the Sars-Cov2 pandemic, the incidence of thymism disorders has significantly increased and, often, patients are reluctant to want to take drugs aimed at stabilizing mood. In order to provide an alternative approach to drug therapies, we have prepared a study in order to evaluate the possibility of improving the quality of life of these subjects through osteopathic treatment. Patients were divided into visceral and fascial manual treatment with the aim of increasing serotonin levels and stimulating the vagus nerve through validated techniques. The results were evaluated through the administration of targeted questionnaires in order to assess quality of life, mood, sleep and intestinal functioning. At a first endpoint we found, in patients undergoing fascial treatment, an increase in quality of life and sleep: in fact, they report a decrease in the number of nocturnal awakenings; a reduction in falling asleep times and greater rest upon waking. In contrast, patients undergoing visceral treatment, as well as those included in the control group, did not show significant improvements. Patients in the fascial group have, in fact, reported an improvement in thymism and subjective quality of life with a generalized improvement in function. Although the study is still ongoing, based on the results of the first endpoint we can hypothesize that fascial stimulation of the vagus nerve with manual and osteopathic techniques may be a valid alternative to pharmacological treatments in mood and sleep disorders.

Keywords: ostheopathy, insomnia, noctural awakening, thymism

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Authors: Nur Hidayah Kaz Abdul Aziz, Norhalida Hashim, Zurina Hassan

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Peripartum period is a time where women are vulnerable to depression, and stress may further increase the risk of its occurrence. Use of selective serotonin reuptake inhibitors (SSRI) in the treatment of postpartum depression is a common practice. Comparison of antidepressant treatment, however, is rarely studied between gestated and nulliparous animals exposed to stress. This study was aimed to investigate the effect of parity and stress, as well as fluoxetine (an SSRI) treatment after stress exposure on the behavior of rats. Gestating and nulliparous Sprague Dawley rats were either subjected to chronic stressors or left undisturbed throughout the gestation period. After parturition, all stressors were stopped and some of the stressed rats were treated with fluoxetine (10mg/kg). Hence, the final groups formed were: 1. Non-stressed nulliparous rats, 2. Non-stressed dams, 3. Stressed nulliparous rats, 4. Stressed dams, 5. Fluoxetine-treated stressed nulliparous rats, and 6. Fluoxetine-treated stressed dams. Rats were tested in open field test (OFT), novel object recognition test (NOR) and forced swim test (FST) after weaning of pups. Gestational stress significantly reduced the locomotor activity of rats in OFT (p<0.05), while fluoxetine significantly increased the activity in nulliparous rats (p<0.001) but not the dams. While no differences were observed in NOR, stress and parity inhibited the rats from performing swimming behavior in FST. However, climbing and immobile behaviors in FST were found to have no significant differences, although there is a tendency of effect of treatment for immobility parameter (p=0.06) where fluoxetine-treated stressed dams were being the least immobile. In conclusion, the effects of parity and stress, as well as fluoxetine treatment, depended on the type of behavioral test performed.

Keywords: stress, parity, SSRI, behavioral tests

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