The Effects of Chronic Asprosin Administration on Sense of Smell and Sexual Behavior in Female Rats.

INTRODUCTION: Asprosin is an adipokine released from white adipose tissue during fasting and acts through the olfactory receptor. It is known that adipokines play roles in reproductive physiology in mammals. However, there are very few studies conducted on role of asprosin in reproductive functions. There are no studies on its relationship with sexual motivation. It was shown in the literature that administration of asprosin to male mice improves olfaction. It is also known that there is a strong correlation between smell and sexual desire. In view of this, it was hypothesized that chronic administration of asprosin would improve olfactory performance and increase sexual incentive motivation in female rats for male partners. METHODS: This hypothesis was tested by applying the hidden cookie test, sexual incentive test, active research test, and sexual behavior test. The changes in serum hormone levels in female rats that chronically received asprosin were also measured and compared. RESULTS: Chronic asprosin exposure increased olfactory performance, male preference ratio, male investigation preference ratio, activity index, and anogenital investigation behavior. Also, serum oxytocin and estradiol levels increased following chronic administration of asprosin in female rats. CONCLUSION: These data suggest that chronic administration of asprosin can result in increased sexual incentive motivation for opposite sex in female rats over increased olfactory performance and changes in reproductive hormones.

Treadmill exercise has healing effects on obesity-induced sexual behavior disorder through kisspeptin and kiss1R expression in male rats.

The basic objective of this study was to examine the possible effects of treadmill exercise on obesity-related sexual behavior disorder in obese male rats and the role of kisspeptin in this effect. The rats were separated from their mothers at the age of 3 weeks, and classified into four groups as Control (C): normal diet-sedentary group, Exercise (E): normal diet-exercise group, Obese (O): high-fat diet-sedentary group, Obese + Exercise (O+E): high-fat diet-exercise grouSexual behavioral testing was conducted in the rats. At the end of the study, brain samples were taken from the animals for gene expression analyses. The treadmill exercise caused a significant increase in the O+E Group compared to the O Group in kisspeptin and kiss1R gene expression and in EF, ML, IL, MF, IF, III, EL, PEI, IR1, MFT, IFT, IRT sexual behavior parameters (p<0.05), and a significant decrease in ML, IL, III, EL sexual behavior parameters (p<0.05). Treadmill exercise caused a significant decrease in EF, ML, IL, MF, IF, III, EL, PEI, IR1, MFT, IFT, IRT sexual behavior parameters and kisspeptin and kiss1R gene expression in the hypothalamus, hippocampus, prefrontal cortex and corpus striatum in E Group compared to C Group (p<0.05), and a significant increase in ML, IL, III, EL sexual behavior parameters (p<0.05). Based on this effect, we believe that it is caused by an increase in kisspeptin and kiss1R expression in the hypothalamus, hippocampus, prefrontal cortex and corpus striatum. In conclusion, treadmill exercise-induced kisspeptin secretion may increase GnRH secretion and cause hypothalamo-pituitary gonadal axis activation and ameliorative effect on deteriorated sexual function.

TRPM2 may be involved in high fructose corn syrup-induced anxiety-like behavior in adult male rats.

Excessive high fructose corn syrup (HFCS) consumption is known to cause oxidative stress, which induces transient receptor potential melastatin type 2 (TRPM2) channel gating. Oxidative stress-induced TRPM2 gating is suggested to play an important role in neurons, indicating a role for the TRPM2 channel in a variety of neuropsychiatric disorders including depression and anxiety. We investigated the effects of HFCS and chronic immobilization stress (CIS) on TRPM2 channel immunoreactivity, anxiety, and depressive-like behaviors in adult male rats. The male rats (n=8/group) were divided into 4 groups: Control, 20% HFCS (F20), 40% HFCS (F40), and stress. The control group received tap water, and F20 and F40 groups were exposed to HFCS 20% and 40% respectively for 14 consecutive days. Rats in the stress group were subjected to immobilization stress for 3 or 6 hours daily in the first and second weeks to induce CIS. Then, light/dark tests, open field tests (OFT), and tail suspension tests (TST) were performed, respectively. In the light/dark test, the time spent in the dark chamber significantly increased in all groups vs the control group (P<0.01). In support of this result, time spent in the light chamber significantly decreased in all groups vs the control group (P<0.01). Besides, CIS significantly increased depressive-like behavior in the stress group vs the control group (P<0.05). In serum hormone levels, corticosterone (CORT) levels significantly increased in the F40 and stress groups vs the control group (P<0.01). TRPM2 immunoreactivity significantly increased in the hippocampus, prefrontal cortex (PFC), nucleus accumbens (NaC), and amygdala regions by HFCS and CIS treatments. For the first time in the present study,  showed that f increased immunoreactivity of the TRPM2 cation channels may be linked to the anxiety-like behavior induced by HFCS.

Irisin Improves High-Fat Diet-Induced Sexual Dysfunction in Obese Male Rats.

INTRODUCTION: Obesity is known to cause sexual dysfunction including erectile dysfunction and poor semen quality. Lifestyle modifications such as exercise have increasingly been more recognized to lower the likelihood of having sexual dysfunction or infertility in obese men. In this context, as an exercise-mimetic hormone, irisin has a potential to improve obesity-related reproductive dysfunctions. We aimed to elucidate possible effects of irisin on high-fat diet (HFD)-induced reproductive dysfunction in obese male rats. METHODS: Rats were divided into four groups: vehicle, irisin, obese, and obese + irisin. The rats in obese and obese+irisin groups were fed with HFD (60% kcal fat) pellets for 12 weeks to induce obesity, and then obesity-induced sexual dysfunction was confirmed by the sexual behavior test (SBT). Irisin and obese+irisin groups received irisin (100 ng/kg/day) infusion by an s.c. osmotic minipump for 4 weeks after HFD-induced obesity was formed. RESULTS: Irisin did improve a number of measures of copulation, including penile erection, ejaculation, and sexual performance, and also improved sperm morphology and motility and decreased fat-induced testicular damage. It decreased serum leptin levels. On the other hand, irisin did not affect serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. It also increased gene expression of tyrosine hydroxylase (TH) and adrenoceptor alpha 1A (ADRA1A) in the medial preoptic area (mPOA) and nucleus accumbens (NAc). CONCLUSION: Irisin provided a marked enhancement of HFD-induced decrease in libido, potency, sexual performance, and erection in SBT. Taken together, our results emphasize that irisin has a restorative and improver role in HFD-induced reproductive dysfunctions in obese male rats.

Interference of gadolinium dechelated from MR contrast agents by calcium signaling in neuronal cells of GnRH.

Contrast agents (CAs) used in magnetic resonance imaging (MRI) are produced by chelating the metal gadolinium (Gd) with organic ligand molecules to form stable complexes. But, Gd3+ may dissociate from the CAs and subsequently might become toxic to its environment. Besides toxicity, it might inhibit calcium channels on cell membranes and this action could be detrimental to the cells governing biological development. The aim of this study was to investigate the interference of Gd3+ dechelated from the CAs by calcium signaling in the neuronal cells of gonadotropin-releasing hormone (GnRH), regulating puberty, and sexual development. The study used the mouse GT1-7 cell line as a model system, and Fura-2 based calcium imaging for detecting the interruption of intracellular calcium transport by the extracellular presence of Gd3+ as released from the CAs; gadodiamide and gadoterate meglumine, when the cells were stimulated in vitro culture by exposure to melatonin.The CA gadoterate meglumine interfered minimally with the calcium signaling, and thus its use is preferable in standard MRI exams. The release of Gd3+ from gadodiamide was significant and becomes of great concern as it may impact the neurophysiology of the neuronal cells in general, and gonadotropin production in particular, even in normal patients without nephrogenic systemic fibrosis. The toxicity induced by the influx of dechelated Gd3+ in the neurons of GnRH would have significant implications for puberty and reproductive functions.

Kisspeptin leads to calcium signaling in cultured rat dorsal root ganglion neurons.

Although kisspeptin and GPR54 have been reported to be expressed in the neurons of the dorsal root ganglion (DRG) of rats, and kisspeptin has been suggested to be involved in pain modulation in rodents, there is no study on the effects and mechanisms of kisspeptin on sensory neurons. Therefore, the aim of this study was to investigate the effects and mechanism of kisspeptin on intracellular free calcium levels in cultured rat DRG neurons. Bath application of kisspeptin-10 increased intracellular free calcium levels ([Ca2+]i). In the absence of extracellular calcium, the kisspeptin induced an attenuated but still significant increase in [Ca2+]i. [Ca2+]i responses persisted in the presence of protein kinase C (PKC) inhibitor. Data from this study revealed that kisspeptin-10 activates [Ca2+]i signaling independent of PKC in cultured rat sensory neurons suggesting that peripheral site is also involved in the pain modulating effect of kisspeptin.

Kisspeptin and RF9 prevent paroxetine-induced changes in some parameters of seminal vesicle fluid in the male rats.

The aim of the study was to examine possible impacts of paroxetine and agomelatine on the levels of some components that constitute the seminal vesicle fluid. As a second purpose, it was also aimed to examine how possible negative effects induced by paroxetine on seminal vesicle fluid components were affected by kisspeptin and RF9 (an RFamide-related peptide antagonist, RFRP). Forty-two male rats, aged 21 days, divided into six groups; control, sham, paroxetine, agomelatine, paroxetine + kisspeptin and paroxetine + RF9. Paroxetine (3.6 mg/kg) and agomelatine (10 mg/kg) were administrated by oral gavage. Kisspeptin (1 nmol) and RF9 (20 nmol) were administered intracerebroventricular (i.c.v). The experiments were ended on post-natal 120 days; fructose, vitamin E, sodium, potassium and magnesium levels were measured in seminal vesicle fluid. Fructose, vitamin E, magnesium and potassium levels were significantly decreased in seminal vesicle fluid from the rats treated with paroxetine but did not show significant differences following agomelatine administration. The co-administration of kisspeptin or RF9 with paroxetine prevented the paroxetine-induced negative effects on seminal vesicle fluid components. These results suggest that reduction in sperm fertilising ability caused by changes in seminal vesicle fluid can be seen in long-term antidepressant use. RF-9 and kisspeptin might have positive effects on long-term antidepressant use-induced infertility.

Agomelatine modulates calcium signaling through protein kinase C and phospholipase C-mediated mechanisms in rat sensory neurons.

Agomelatine, a novel antidepressant exerting its effects through melatonergic and serotonergic systems, implicated to be effective against pain including neuropathic pain but without any knowledge of mechanism of action. To explore the possible role of agomelatine on nociceptive transmission at the peripheral level, the effects of agomelatine on intracellular calcium ([Ca2+ ]i ) signaling in peripheral neurons were investigated in cultured rat dorsal root ganglion (DRG) neurons. Using the fura-2-based calcium imaging technique, the effects of agomelatine on [Ca2+ ]i and roles of the second messenger-mediated pathways were assessed. Agomelatine caused [Ca2+ ]i signaling in a dose-dependent manner when tested at 10 and 100 µM concentration. Luzindole, a selective melatonin receptor antagonist, almost completely blocked the agomelatine-induced calcium signals. The agomelatine-induced calcium transients were also nearly abolished following pretreatment with the 100 ng/ml pertussis toxin, a Gi/o protein inhibitor. The stimulatory effects of agomelatine on [Ca2+ ]i transients were significantly reduced by applications of phospholipase C (PLC) and protein kinase C (PKC) blockers, 10 µM U73122, and 10 µM chelerythrine chloride, respectively. The obtained results of agomelatine-induced [Ca2+ ]i signals indicates that peripheral mechanisms are involved in analgesic effects of agomelatine. These mechanisms seems to involve G-protein-coupled receptor activation and PLC and PKC mediated mechanisms.

Lipopolysaccharide reduces gonadotrophin-releasing hormone (GnRH) gene expression: role of RFamide-related peptide-3 and kisspeptin.

RFamide-related peptide (RFRP)-3 reduces luteinising hormone (LH) secretion in rodents. Stress has been shown to upregulate the expression of the RFRP gene (Rfrp) with a concomitant reduction in LH secretion, but an effect on expression of the gonadotrophin-releasing hormone (GnRH) gene (Gnrh1) has not been shown. We hypothesised that lipopolysaccharide (LPS)-induced stress affects expression of Rfrp, the gene for kisspeptin (Kiss1) and/or Gnrh1, leading to suppression of LH levels in rats. Intracerebroventricular injections of RFRP-3 (0.1, 1, 5 nmol) or i.v. LPS (15µgkg-1) reduced LH levels. Doses of 1 and 5 nmol RFRP-3 were then administered to analyse gene expression by in situ hybridisation. RFRP-3 (5 nmol) had no effect on Gnrh1 or Kiss1 expression. LPS stress reduced GnRH and Kiss1 expression, without affecting Rfrp1 expression. These data indicate that LPS stress directly or indirectly reduces Gnrh1 expression, but this is unlikely to be due to a change in Rfrp1 expression.

Effects of long-term paroxetine or bupropion treatment on puberty onset, reproductive and feeding parameters in adolescent male rats.

Antidepressant use in adolescents has become more common in recent years. We have found several studies stating that prenatal antidepressant exposure can lead to delayed or earlier puberty onset but there was no study on postnatal paroxetine or bupropion. The main aim of this study was to investigate the effect of postnatal exposure to bupropion or paroxetine on puberty onset, reproductive and feeding results. The male rats (n = 8/group) aged 21 days were exposed to paroxetine (3.6 mg/kg) or bupropion (17 mg/kg) orally by gastric gavage every day from postnatal day 21-90. Also, control group received only saline orally as a vehicle. Postnatal exposure to bupropion or paroxetine delayed puberty onset compared to control group, but it was not significant. Sperm counts were significantly lower in the paroxetine and bupropion groups compared to control group. Sperm motility was significantly lower in only bupropion group. In addition, sperm motility was lower in paroxetine group, but it was not significant. In the histopathological examination, there was damage to the testicular structure in both treatments. Taken together, our result indicates that postnatal paroxetine or bupropion exposure may affect puberty onset and contribute to the impairment in fertility in male rats.

The effects of apelin on myometrium contractions in pregnant rats.

Apelin, which is a new hormone, is secreted especially in the brain by hypothalamus as well as by many other organs like the stomach, fat tissue, and the heart. For apelin, whose possible effects on many bodily functions like the endocrine system, cardiovascular system and metabolic activities are still under investigation, the reproductive system is also an important target area. The purpose of the present study was to investigate the effects of plasma apelin levels in rats that were in diestrus, pregnancy and lactation periods, and to examine its possible effects on myometrium contractions of pregnant rats and non-pregnant rats that were in diestrus period.  The plasma apelin concentrations in female adult Wistar rats were determined with the ELISA method in the diestrus period, and on the 12th, 18th, and 21st days of the pregnancy, and on the 2nd and 10th days of lactation (n=7 for each group). In addition, the effect of apelin at 0.01, 0.1, 1 and 10 µM doses on isometric contractions in the rat uterus on the 21st day of pregnancy and in diestrus period was tested by using isolated organ bath. This protocol was repeated under conditions that were pre-treated with protein kinase C inhibitor in calcium-free medium, and the possible effect of apelin on contractions and the mechanisms that might mediate this effect were investigated. When plasma apelin levels were compared with the rats in diestrus period, the apelin concentrations in the 21-day pregnancy group were high at a significant level (p<0.05); and low at a significant level in the 2-day lactation group (p<0.05). In myometrium contraction trials, it was observed that apelin induced the contractions. Apelin increased the frequency of the myometrium contractions at a significant level when applied at 1 µM and 10 µM concentrations (p<0.05 and p<0.001). Only after the apelin application at 10 µM concentration did the amplitude of the contractions increase at a significant level (p<0.01). In the myometrium of the rats that were on the 21st day of pregnancy, the frequency of the contractions was statistically significant at 0.1 µM, 1 µM and 10 µM doses (p<0.01). In addition, the amplitude of the contractions increased at a statistically significant level at 1 µM and 10 µM dose application (p<0.05 and p<0.01, respectively). The apelin application induced the contractions in calcium-free medium. When apelin was applied after the pre-application with protein kinase C inhibitor, no contractions were observed. The present study showed that apelin levels were increased at the end of pregnancy in rats, and the hormone induced the uterus contractions. This effect does not occur with protein kinase C inhibitor and in calcium-free medium, which shows that protein kinase C pathway might play a role in these mechanism.  These findings show that apelin might be an endogenous peptide that plays a role on uterine contractions at birth in rats.

Pinealectomy alters IFN-γ and IL-10 levels in primary thymocyte culture of rats.

Melatonin, produced mainly by the pineal gland, has an immunomodulatory role. However, the effects of the pineal gland and/or melatonin on thymus cytokine levels such as interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-10 are not well known. Twenty-one male Wistar rats (220-250 gr) were randomly divided into three groups (n=7): intact control, sham, and pinealectomy. Primary thymocyte cultures were prepared from each group and dispensed into well plates as Control, DMSO (or vehicle), Sham-pinealectomy, Pinealectomy, Pinealectomy+10µM melatonin, and Pinealectomy+100µM melatonin. IFN-γ, IL-4, and IL-10 concentrations were measured in the thymocytes (as nonstimulated and Concanavalin A-stimulated) after 24 h. IFN-γ levels significantly increased and IL-10 levels significantly decreased in both media prepared from pinealectomized rats. There was no significant difference between the groups in terms of IL-4. In the pinealectomy+10µM melatonin group, IFN-γ and IL-10 levels did not differ from the pinealectomy group. However, the dose of 100µM melatonin caused a decrease in levels of IFN-γ in both thymocyte media and an increase in the concentration of IL-10 in Concanavalin A-stimulated thymocytes. In conclusion, pineal gland and/or melatonin affect IFN-γ and IL-10 levels in the thymus gland.

Kisspeptin increases intracellular calcium concentration by protein kinase C-mediated signaling in the primary cultured neurons from rat hippocampus.

In addition to the fact that kisspeptin and its receptor GPR54 are well known to be abundantly expressed in the hypothalamus with suggestive roles in the initiation of puberty and similar reproductive system properties, there is also proof showing that kisspeptin might have influences on hippocampal functions. In our previous study, it was shown that kisspeptin increased free intracellular Ca2+ values ([Ca2+]i) through protein kinase C (PKC) activation in GT1-7 cells. For this reason, we examined the influences of kisspeptin on [Ca2+]i in hippocampal neurons to determine if kisspeptin shows its effects on hippocampus through the same mechanism. Hippocampal neurons were excised from the brains of fetuses on 17th embryonic day from maternal rats. The influences of kisspeptin on [Ca2+]i in hippocampal neurons were examined through in vitro calcium imaging system. The responses of [Ca2+]i to kisspeptin were quantified by the changes in 340nm/380nm ratio.  Kisspeptin-10 caused [Ca2+]i transients in hippocampal neurons. The change in [Ca2+]i by 100 nM kisspeptin was prevented by pre-treating the cells in PKC inhibitor chelerythrine chloride. According to the results, kisspeptin activates intracellular calcium signaling in hippocampal neurons via the pathway that depends on PKC. The results of this study suggest that kisspeptin may have a role in hippocampal neuron functions.

Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats.

The aim of this study was to determine the modulatory effects of peptide 234 (p234) (an antagonist of GPR54 receptors) on kisspeptin and RF9 (an RFamide-related peptide antagonist)-induced changes in reproductive functions and energy balance in female rats. Female Sprague-Dawley rats were weaned on postnatal day (pnd) 21. The animals were intracerebroventricularly cannulated under general anesthesia on pnd 23. Groups of female rats were injected with kisspeptin, RF9, p234, kisspeptin plus p234, or RF9 plus p234, daily. The experiments were ended on the day of first diestrus following pnd 60. Kisspeptin or RF9 alone advanced vaginal opening (VO), which was delayed by administration of kisspeptin antagonist alone. In the rats given kisspeptin plus p234 or RF9 plus p234, VO was not different from control rats. Kisspeptin and RF9 elicited significant elevations in circulating LH levels. Coadministrations of kisspeptin or RF9 with p234 decreased LH levels significantly. The use of p234 alone did not cause any significant change in LH secretion. Kisspeptin decreased both food intake and body weight while RF9 decreased only food intake without affecting body weight. The effects of kisspeptin on energy balance were also reversed by central administration of p234. In conclusion, kisspeptin antagonist, p234, modulates the effects of kisspeptin on reproductive functions and energy balance, whereas RF9 seems to exert only its effects on reproductive functions by means of GPR54 signaling in female rats.

Percentages of serum, liver and adipose tissue fatty acids and body weight are affected in female rats by long-term Central kisspeptin treatments.

This study was conducted to determine the possible effects of long-term exogenous kisspeptin and its antagonist P234 on serum, liver and adipose tissue fatty acids (FA) profiles, as well as body weight, in female rats. Kisspeptin (50 pmol) and P234 (1 nmol) were administrated to the weaned Sprague-Dawley female rats by an intracerebroventricular injection from the 26th postnatal day to the 60th postnatal day. Percentages of the serum total saturated FA (∑SFA) and total monounsaturated FA (∑MUFA) were lower in the kisspeptin group. In the adipose tissue, ∑SFA was lower and total unsaturated FA higher in the P234 group. Moreover, long-term central kisspeptin injection caused a decrease in the body weight. When compared to the kisspeptin group, the final body weights were higher in the P234 and kisspeptin + P234 groups. According to our results, we suggest that kisspeptin has a regulatory role in FA metabolism and regulation of body weight.

Treadmill Exercise Improves Behavioral and Neurobiological Alterations in Restraint-Stressed Rats.

Stress is a state that is known to impact an organism's physiological and psychological balance as well as the morphology and functionality of certain brain areas. In the present work, chronic restraint stress (CRS) model rats treated with treadmill exercise were used to examine anomalies associated to emotion and mood as well as molecular changes in the brain. Forty male Sprague-Dawley rats were divided into control, stress, exercise, and stress+exercise groups. CRS were exposed to stress group rats and exercise group underwent a chronic treadmill exercise. Depressive-like behavior was evaluated with the forced swim test (FST) and tail suspension test (TST). For assessing anxiety-like behavior, the light-dark test (LDT) and the open field test (OFT) were used. The Morris water maze test (MWMT) was used for testing memory and learning. Brain's monoamine level and the expression of genes related to stress were measured. It was discovered that CRS lengthens latency in the MWMT, increases immobility in the FST and TST, decreases time in the light compartment, and causes hypoactivity in the OFT. CRS reduced the dopamine levels in the nucleus accumbens(NAc). Brain-derived neurotrophic factor (BDNF), dopamine receptors, and serotonin receptor (HTR2A) gene expression in the prefrontal cortex, corpus striatum, and hypothalamus were decreased by CRS. Exercise on a treadmill leads to increase NAc's dopamine and noradrenaline levels and prevented behavioral alterations. Exercise increased the alterations of BDNF expressions in the brain in addition to improving behavior. As a result, CRS-induced behavioral impairments were effectively reversed by chronic treadmill exercise with molecular alterations in the brain.

Asprosin, a novel glucogenic adipokine: a potential therapeutic implication in diabetes mellitus.

OBJECTIVES: We aimed to investigate the effects of asprosin on diabetes with a focus on serum glucose, irisin, ghrelin, leptin levels and hepatic levels of triglycerides (TG), cholesterol, low-density lipoprotein (LDL). METHODS: Asprosin (10 µg/kg) was administered intraperitoneally four times at 3-day intervals and then blood and hepatic parameters above mentioned were investigated in control and diabetic mice. RESULTS: The administration of asprosin increased blood glucose level in healthy animals (p = .05) whereas it did not change blood glucose level in diabetic animals. In addition, while asprosin decreased irisin level and increased ghrelin level, it did not change leptin level in diabetic mice. Therewithal, asprosin decreased the increasing levels in hepatic TG, cholesterol, and LDL in diabetic mice. CONCLUSIONS: Our novel findings implicate that asprosin may be a target molecule in preventing the development and complications of diabetes.

Treadmill exercise training improves the high-fat diet-induced behavioral changes in the male rats.

The purpose of this study was to investigate the effects of treadmill exercise training on obesity-induced behavioral changes in high-fat diet (HFD)-induced male rats. In this study, 40 male Sprague-Dawley rats were divided into 4 groups after they were weaned: Control (C), Exercise (E), Obese (O) and Obese + Exercise (O + E). For the obesity model % 60 high-fat diet were applied. After obesity was induced, rats were either moderate aerobic exercise (treadmill running) trained or left untrained. Different tasks to assess spatial learning and memory (Morris water maze test (MWMT)), depressive-like behavior (forced swimming test(FST), tail suspension test (TST) and anxiety-like behavior (light-dark test (LDT) and open field test (OFT)) were conducted. Exercise caused a significant reduction in duration of immobility in the O group in FST and the decrease in immobility in the O + E rats in TST. The O + E rats demonstrated a significant increase in the time spent in the light box as compared to the O group in the LDT. The O + E rats did not show any behavioral alterations as compared to all the other groups in the OFT. In the O + E group, there was a significant increase in the time spent in the target quadrant compared to the O group in the MWMT. Our results support that treadmill exercise could improve cognitive, depressive-like, anxiety-like behavioral changes in the HFD-induced obese rats.

Agomelatine, A Potential Multi-Target Treatment Alternative for Insomnia, Depression, and Osteoporosis in Postmenopausal Women: A Hypothetical Model.

Insomnia, which is associated with menopausal depression, is a common symptom of menopause. Both symptoms have a common etiology, and can affect each other significantly. Pharmacological interventions, including hypnotics and antidepressants, and non-pharmacological therapies are generally administered in clinical practice for insomnia treatment. As another menopausal disorder, osteoporosis is described as a disease of low bone mineral density (BMD), affecting nearly 200 million women worldwide. Postmenopausal osteoporosis is common among middle-aged women. Since postmenopausal osteoporosis mainly results from low estrogen levels, menopausal hormone therapy (HT) is considered the first-line option for the prevention of osteoporosis during the menopausal period. However, almost no study has evaluated novel treatments for the combined prevention of insomnia, depression, and osteoporosis. Hence, it is necessary to develop new multi-target strategies for the treatment of these disorders to improve the quality of life during this vulnerable period. Melatonin is the major regulator of sleep, and it has been suggested to be safe and effective for bone loss therapy by MT-2 receptor activity. As a result, we hypothesize that agomelatine, an MT-1 and MT-2 receptor agonist and 5-HT2C receptor antagonist, holds promise in the combined treatment of insomnia, depression, and osteoporosis in middle-aged women during menopause.

Chronic exposure to paroxetine or bupropion modulates the pubertal maturation and the reproductive system in female rats.

Antidepressant drugs are globally used to treat several psychiatric disorders in pediatric patients and their prescription has continued to increase in recent years, especially among girls. In addition to its well-known metabolic and gastrointestinal side effects, antidepressants can cause sexual dysfunction in adults. However, the effects of the antidepressants on puberty onset and reproductive system remain unclear in children and adolescents. Therefore, the goal of this study is to examine the effects of chronic postnatal antidepressant drugs, paroxetine or bupropion, treatments on puberty onset and reproductive system components in female rats weaned at postnatal day (PND) 21. Female rats (n = 10 for each group) were exposed to vehicle (0.2 mL of saline), paroxetine (3.6 mg/kg in 0.2 mL of saline) or bupropion (17 mg/kg in 0.2 mL of saline) daily by oral gavage from the PND 21 to PND 90-93. Chronic paroxetine or bupropion treatments advanced the puberty onset, but the difference was statistically significant in only the paroxetine group. The exposure to bupropion significantly decreased the serum anti-Müllerian hormone (AMH) levels and luteinizing hormone (LH) levels. There were increases in serum estradiol levels by both antidepressant treatments and the significance was found in only the paroxetine group. Consistent with these results, histopathologic changes were observed in the ovary and uterus tissues taken from both antidepressant-treated rats. The obtained results of chronic postnatal exposure to paroxetine or bupropion may change the timing of puberty onset and lead to disruption of reproductive functions in females.