Antidepressant Effect In Rats Research Articles

Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: II. Antidepressant Effect in an Experimental Animal Model.

Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Quercetin (QER) demonstrated antidepressant effects in rats exhibiting anxiety and depressive-like behaviors. In an attempt to improve QER's antidepressant activity, a QER-loaded transferosome (QER-TFS) thermosensitive gel for intranasal administration was formulated and optimized. The therapeutic effectiveness of the optimized formulation was assessed in a depressed rat model by conducting a behavioral analysis. Behavioral study criteria such as immobility, swimming, climbing, sucrose intake, number of crossed lines, rearing, active interaction, and latency to feed were all considerably enhanced by intranasal treatment with the QER-TFS in situ gel in contrast to other formulations. A nasal histopathological study indicated that the QER-TFS thermosensitive gel was safe for the nasal mucosa. An immunohistochemical analysis showed that the animals treated with the QER-TFS thermosensitive gel had the lowest levels of c-fos protein expression, and brain histopathological changes in the depressed rats were alleviated. According to pharmacodynamic, immunohistochemical, and histopathological experiments, the intranasal administration of the QER-TFS thermosensitive gel substantially alleviated depressive symptoms in rats. However, extensive preclinical investigations in higher animal models are needed to anticipate its effectiveness in humans.

Preclinical Screening of Antidepressant Activity of Formulated Sertraline Hydrochloride-Loaded Solid Lipid Nanoparticles in Rats

Objective: The main goal of our study was to investigate the antidepressant activity of Formulated Sertraline hydrochloride-loaded Solid Lipid Nanoparticles (SLNPs) by using a rat forced swimming test (FST) and tail suspension test (TST).
 Materials and Methods: Animals were divided into three groups, consisting of six rats in each group. Out of these, one group served as control that received distilled water, second group was standard received Sertraline HCl (20 mg/kg intranasal) and third group was received test formulation (SLNPs 50 mg/kg intranasal). To assess the effect of SLNPs on immobility activity through FST and TST were used to take as a measure of antidepressant activity.
 Results: SLNPs reduced the immobility duration in TST as well as in FST. In both methods, there was a statistical significant decrease in immobility of SLNPs group when compared to the control group.
 Conclusion: The results suggested that SLNPs produced significant antidepressant effect in rats which was comparable with control group and standard Sertraline HCl group animals.

Neuronal activities during palatable food consumption in the reward system of binge-like eating female rats

Binge eating disorder (BED), characterized by bingeing episodes and compulsivity, is the most prevalent eating disorder; however, little is known about its neurobiological underpinnings. In humans, BED is associated with desensitization of the reward system, specifically, the medial prefrontal cortex (mPFC), nucleus accumbens (Acb), and ventral tegmental area (VTA). Additionally, BED patients feel relieved during bingeing, suggesting that bingeing helps to decrease the negative emotions they were feeling prior to the binge episode. However, the mechanisms that underlie this feeling of relief in BED patients have not been well investigated. To investigate neuronal activity before and during palatable food consumption in BED, we performed in vivo electrophysiological recordings in a binge-like eating rat model (bingeing, n = 12 and non-bingeing, n = 14) and analyzed the firing rate of neurons in the mPFC, Acb, and VTA before and during access to sucrose solution. We also investigated changes in the firing rate of neurons in these regions during and between active bingeing, which may underlie the feeling of relief in BED patients. We found that neuronal firing rates of mPFC and VTA neurons in bingeing rats were lower than those in non-bingeing rats before and during sucrose consumption. Palatable food consumption increased neuronal firing rates during and between active bingeing in bingeing rats. Our results suggest a desynchronization in the activity of reward system regions, specifically in the mPFC, in bingeing rats, which may also contribute to BED. These results are consistent with those of functional magnetic resonance imaging (fMRI) studies that reported decreased activity in the reward system in BED patients. We propose that increased neuronal activity in the mPFC, Acb, or VTA produces an antidepressant effect in rats, which may underlie the sense of relief patients express during bingeing episodes.

Reduced neuroinflammation and enhanced neurogenesis following chronic agomelatine treatment in rats undergoing chronic constant light

Experimental studies have revealed the involvement of neuroinflammation mediated by activated microglia in the pathophysiology of depression, suggesting a novel target for treatment. The atypical antidepressant Agomelatine (Ago) has an advantage compared to the classical antidepressants due to its chronobiotic activity and unique pharmacological profile as a selective agonist at the melatonin receptors and an antagonist at the 5HT2C receptors. We have recently revealed that Ago can exert a potent antidepressant effect in rats exposed to a chronic constant light (CCL). In the present study, we hypothesized that the anti-inflammatory activity of this melatonin analog on activated neuroglia in specific brain structures might contribute to its antidepressant effect in this model. Chronic Ago treatment (40 mg/kg, i.p. for 21 days) was executed during the last 3 weeks of a 6-week period of CCL exposure in rats. The CCL-vehicle-treated rats showed a profound neuroinflammation characterized by microgliosis and astrogliosis in the hippocampus, basolateral amygdala (BL) and partly in the piriform cortex (Pir) confirmed by immunohistochemistry. With the exception of the Pir, the CCL regime was accompanied by neuronal damage, identified by Nissl staining, in the hippocampus and basolateral amygdala and impaired neurogenesis with reduced dendritic complexity of hippocampal neuroprogenitor cells detected by doublecortin-positive cells in the dentate gyrus (DG) subgranular zone compared to the control group. Ago reversed the gliosis in a region-specific manner and partially restored the suppressed DG neurogenesis. Ago failed to produce neuroprotection in CCL exposed rats. The present results suggest that the beneficial effects of Ago represent an important mechanism underlying its antidepressant effect in models characterized by impaired circadian rhythms.

N-3 PUFA Have Antidepressant-like Effects Via Improvement of the HPA-Axis and Neurotransmission in Rats Exposed to Combined Stress.

Early life and adulthood stress increase vulnerability for mental illness, and eventually trigger depression. N-3 polyunsaturated fatty acids (PUFA) have antidepressant effects, but their effect on rats exposed to combined stress has been not investigated. This study aimed to investigate whether n-3 PUFA supplementation had antidepressant-like effects in rat models of depression induced by a combination of chronic mild stress (CMS) and maternal separation (MS) through the modulation of the hypothalamic-pituitary-adrenal (HPA) axis and neurotransmission. Rats were fed the n-3 PUFA diet during the pre-weaning or post-weaning period or for lifetime, and allocated to different groups based on the type of induced stress: non-stress (NS), CMS + MS, or CMS alone. N-3 PUFA improved the depressive behaviors of the CMS alone and CMS + MS groups and modulated the HPA-axis by reducing the circulating adrenocorticotropic hormone, corticosterone, and corticotropin-releasing factor expression, and increasing glucocorticoid receptor expression. N-3 PUFA also modulated brain phospholipid fatty acid concentration, thus reducing inflammatory cytokines; improved the serotonergic pathway, thus increasing the expression of the brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), serotonin-1A receptor, and serum levels of serotonin; but did not affect glutamatergic neurotransmission. Furthermore, n-3 PUFA decreased the hippocampal expression of microRNA-218 and -132, increased that of microRNA-155, and its lifetime supplementation was more beneficial than pre- or post-weaning supplementation. This study suggests that n-3 PUFA has an antidepressant effect in rats exposed to combined stress, through the improvement of the HPA-axis abnormalities, the BDNF-serotonergic pathway, and the modulation of microRNAs.

Antidepressant-Like Effects of Hesperidin in Animal Model of Post-Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder characterized by depression and anxiety, that arises due to an imbalance of neurotransmitters in response to excessive stress. Hesperidin (HSD) is a naturally occurring flavonoid shown to exert a variety of biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. This study was used the open field test (OFT) and forced swimming test (FST) to examine the effects of HSD on the depression-like response of rats after exposure to a single prolonged stress (SPS) leading to the dysregulation of the serotonergic activation system. Male rats were given HSD (20, 50, and 100 mg/kg, intraperitoneal injection, n=6-7 per group) once daily for 14 days after exposure to SPS. The influence of administration of HSD on SPS-induced behavioral responses and concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and monoamine oxidase-A (MAO-A) in the rat brain were also investigated using enzyme-linked immunoassays (ELISAs). Daily HSD administration signifificantly improved depression-like behaviors in the FST (P0.05), increased the number of lines crossed in the central zone of the OFT (P0.01), and reduced freezing behavior both in contextual and cued fear conditioning. HSD treatment also attenuated the reduction in SPS-induced 5-HT concentrations in the hippocampus and amygdala. This increase in 5-HT concentrations during HSD treatment was partially attributed to a decrease in the 5-HIAA/5-HT ratio in the hippocampus of rats with PTSD. Furthermore, HSD treatment inhibited activity of MAO-A and decreases of tryptophan hydroxylase-1 expression in the hippocampus. HSD was shown to exert antidepressant effects in rats exposed to SPS, suggesting that this natural flflavonoid may be an effective medicine for PTSD.

Umbelliferone modulates depression-like symptoms by altering monoamines in a rat post-traumatic stress disorder model.

Post-traumatic stress disorder (PTSD) is a debilitating psychological disease that is triggered by traumatic events. It is known to cause various complications, including anxiety and depression. Umbelliferone (UMB) is a natural product of the coumarin family. This substance has been reported to exert antioxidant, anti-inflammatory, neuroprotective, and other biological effects. We used the open field test (OFT) and the forced swimming test (FST) to examine the effects of UMB on depression-like symptoms in rats after exposure to a single prolonged stress (SPS), which led to dysregulated activation of the serotonergic system. Male rats were given UMB (20, 40, or 60mg/kg, intraperitoneal injection) once daily for 14days after exposure to an SPS. Daily UMB administration significantly improved depression-like behaviors on the FST, increased the number of lines crossed in the central zone of the OFT, and reduced freezing behavior in both contextual and cued fear conditioning. UMB treatment attenuated the SPS-induced decrease in serotonin (5-HT) concentrations in the hippocampus and amygdala. The increased 5-HT concentration during UMB treatment was partially due to a decrease in the ratio of 5-hydroxyindoleacetic acid/5-HT in the hippocampus of rats with PTSD. According to our results, UMB has an antidepressant effect in rats exposed to an SPS, suggesting that this natural product of the coumarin family can be used to effectively treat PTSD.

Korean Red Ginseng prevents posttraumatic stress disorder–triggered depression-like behaviors in rats via activation of the serotonergic system

BackgroundPosttraumatic stress disorder (PTSD), a mental disorder induced by traumatic stress and often accompanied by depression and/or anxiety, may involve an imbalance in the neurotransmitters associated with the fear response. Korean Red Ginseng (KRG) has long been used as a traditional medicine and is known to be involved in a variety of pharmacological activities. We used the open field test and forced swimming test to examine the effects of KRG on the depression-like response of rats after exposure to single prolonged stress (SPS), leading to activation of the serotonergic system. MethodsMale rats received KRG (30, 50, and 100 mg/kg, intraperitoneal injection) once daily for 14 days after exposure to SPS. ResultsDaily KRG administration significantly improved depression-like behaviors in the forced swimming test, increased the number of lines crossed and time spent in the central zone in the open field test, and decreased freezing behavior in contextual and cued fear conditioning. KRG treatment attenuated SPS-induced decreases in serotonin (5-HT) tissue concentrations in the hippocampus and medial prefrontal cortex. The increased 5-HT concentration during KRG treatment may be partially attributable to the 5-hydroxyindoleacetic acid/5-HT ratio in the hippocampus of rats with PTSD. These effects may be caused by the activation of hippocampal genes encoding tryptophan hydroxylase-1 and 2 mRNA levels. ConclusionOur findings suggest that KRG has an antidepressant effect in rats subjected to SPS and may represent an effective use of traditional medicine for the treatment of PTSD.

Ginsenoside Rg1 attenuates chronic unpredictable mild stress-induced depressive-like effect via regulating NF-κB/NLRP3 pathway in rats.

Ginsenoside (GS Rg1), which has neuroprotection and anti-inflammation activities, is the main active ingredient of Radix Ginseng. However, its antidepressant-like effect in rats remains unclear. Our study was conducted to investigate whether GS Rg1 confers an antidepressant effect in rats exposed to a chronic unpredictable mild stress model of depression and to explore its possible mechanisms. Our results revealed that GS Rg1 treatments for 3 weeks alleviated the depression-related behaviors of chronic unpredictable mild stress-exposed rats, as indicated by increasing sucrose preference, improving locomotor activity and shortening immobile time in both the forced swimming tests and tail suspension tests. And these ameliorative effects of GS Rg1 treatment were involved with regulating chronic unpredictable mild stress-induced pro-inflammatory cytokine interleukin beta (IL-1β) related neuro-inflammation. In addition, we further found that GS Rg1 reversed chronic unpredictable mild stress-induced IL-1β elevation, possibly by inhibiting nuclear factor kappa B pathway activation and regulating nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome expression. In short, our results suggested that GS Rg1 exerted a potential antidepressant-like effect in chronic unpredictable mild stress rat model of depression, which may provide an insight into the potential of GS Rg1 in therapeutic implications for depression.

Ginsenoside compound K inhibits oxidative stress and NLRP3 inflammasome activity in mice exposed to chronic unpredictable mild stress

Depression, a mood disorder characterized by persistently low mood and feeling of sadness, has been a more and more serious problem today. NLRP3 (the NACHT, LRR and PYD domains-containing protein 3) inflammasome-mediated central inflammation is recently considered to contribute to the pathology of depression. Based on previous findings that ginsenoside compound K (CK), a ginsenoside metabolite, exhibited antidepressant effects in rats, here we studied whether the antidepressant effects of CK are associated with inhibiting the oxidative stress, NLRP3 inflammasome or inflammatory cytokine in hippocampus of mice exposed to chronic unpredictable mild stress (CUMS). CK (3, 10 and 30 mg/kg) was intragastrically administered for 4 weeks. The depression-like behaviors, oxidative stress parameters, inflammatory cytokines and NLRP3 expression in the hippocampus were evaluated. The results showed that after 4 weeks of administration, CK (30 mg/kg) alleviated the depressant-like behaviors, including shorter immobility time in both the forced swimming test and the tail suspension test, and increased the sucrose preference. In addition, the levels of IL-1β, IL-18 in the hippocampus were significantly decreased in CK-treated groups. The western blot and immunohistochemistry results revealed that the expression levels of NLRP3 inflammasome components (NLRP3 and cleaved caspase-1) were down-regulated in hippocampus of CK-treated mice. These results demonstrate that the antidepressant effect of CK is, at least partially, associated with suppression of oxidative stress-induced NLRP3 inflammasome activation and inhibition of the release of corresponding inflammatory cytokines in the hippocampus.

Bafilomycin A1 alleviates depression‑like symptoms in chronic unpredictable mild stress rats.

Major depression is a multifactorial disease. Emerging evidence has suggested that autophagy is involved in the pathological process of depressive disorders. BafilomycinA1 (BafA1), is an inhibitor of vacuolar H+‑ATPase that is frequently used at high concentrations to block late‑phase autophagy. However, whether BafA1 has antidepressant effects remains to be elucidated. The current study aimed to evaluate the antidepressant effects of BafA1 in rats with chronic unpredictable mild stress (CUMS) and its potential mechanism. The CUMS animal model was established. The sucrose preference test, open‑field test (OFT) and forced swim test (FST) were applied to evaluate the depressive behavior. Synaptic plasticity‑associated proteins synaptophysin and postsynaptic density protein 95 were measured by western blotting and immunofluorescence. Apoptosis‑ and autophagy‑associated proteins in addition to pro‑inflammatory cytokines, including interleukin‑1β and tumor necrosis factor‑α, were detected by western blotting, reverse transcription‑quantitative polymerase chain reaction or ELISA. A 4‑week treatment period with BafA1 markedly ameliorated CUMS‑induced behavioral abnormalities, including increasing sucrose intake, improving locomotor activity in the OFT, and decreasing immobility time in the FST. In addition, treatment with BafA1 restored the dysregulation of synaptic plasticity and inhibited neuroinflammation in rats exposed to CUMS. Furthermore, BafA1 decreased the levels of apoptosis‑ and autophagy‑associated proteins induced by CUMS. The present study demonstrated that BafilomycinA1 resulted in antidepressant effects in rats, which may be mediated by the reversal of apoptosis, autophagy and neuroinflammation in the hippocampus.

Honokiol Exerts Antidepressant Effects in Rats Exposed to Chronic Unpredictable Mild Stress by Regulating Brain Derived Neurotrophic Factor Level and Hypothalamus-Pituitary-Adrenal Axis Activity.

Honokiol (HNK), the main active component of Magnolia officinalis, has shown a variety of pharmacological activities. In the present study, we measured the antidepressant-like effects of HNK in a rat model of chronic unpredictable mild stress (CUMS) and explored its possible mechanisms. The antidepressant-like effects of HNK were assessed in rats by an open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Then, serum levels of corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) and hippocampal brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor α (GRα) levels were assessed to explore the possible mechanisms. We identified that HNK treatment (2, 4, and 8mg/kg) alleviated the CUMS-induced behavioural deficits. Treatment with HNK also normalized the CUMS-induced hyperactivity of the limbic hypothalamic-pituitary-adrenal (HPA) axis, as indicated by reduced CRH, ACTH and CORT serum levels. In addition, HNK increased the expression of GRα (mRNA and protein) and BDNF (mRNA and protein) in the hippocampus. These data confirmed the antidepressant-like effects of HNK, which may be related to its normalizing the function of the HPA axis and increasing the BDNF level in the hippocampus.

Neural cell adhesion molecule peptide mimetics modulate emotionality: pharmacokinetic and behavioral studies in rats and non-human primates.

Recent evidence highlights the fibroblast growth factor (FGF) family in emotion modulation. Although ligands that activate FGF receptors have antidepressant and anxiolytic effects in animal models, FGF ligands have a broad range of actions both in the brain and the periphery. Therefore, identifying molecular partners that may function as allosteric modulators could offer new avenues for drug development. Since neural cell adhesion molecule (NCAM) activates FGF receptors, we asked whether peripherally administered NCAM peptide mimetics penetrate the brain and alter the behavior of standardized tests that have predictive validity for drug treatments of anxiety or depression. The NCAM peptide mimetic, plannexin, acutely increased and chronically decreased anxiety, but did not have antidepressant effects in rats. Another NCAM peptide mimetic, FGLL, had acute anxiogenic effects and chronic antidepressant effects in rats. A related NCAM peptide mimetic, FGLS, had antidepressant effects without modulating anxiety-like behavior, and these antidepressant effects were blocked by an AMPA receptor antagonist. Cisternal cerebrospinal fluid (CSF) levels of FGLs correlated with blood plasma levels in rats and non-human primates, and CSF-to-blood ratios of FGLS were comparable in both species. Results indicate that NCAM peptide mimetics penetrate the brain and support the suggestion that FGLS may be a candidate for further development as a novel treatment for major depressive disorder in humans.

Determination of antidepressant activity of <i>Cyperus rotundus</i> L extract in rats

Purpose: To investigate the antidepressant effect of Cyperus rotundus L. extract (CRLE) in rats.Methods: A rat model of depression was prepared for behavioral tests including tail suspension test or forced swimming test. Wistar rats were randomly divided into six groups (n = 10): normal group (0.9 % NaCl), model group (0.9 % NaCl), positive drug group (fluoxetine 30 mg/kg) as well as CRLE groups, namely, 200, 400 and 800 mg/kg doses. All drugs were orally administered at 14: 00 - 15: 00 h for 1, 7 and 14 days, respectively. Tail suspension and forced swimming tests were conducted 1 h after the last treatment. Monoamine oxidize A (MAO) assay was commenced in rats after 14-day administration. Except for the rats in normal group, other group participated in the behavioral tests.Results: The effect of 800 mg/kg CRLE was more potent than the positive drug fluoxetine. CRLE (≥ 200 mg/kg) treatment for 14 days significantly inhibited brain MAO activity in rats (p < 0.01) in a dosedependent manner. Oral administration of 800 mg/kg CRLE produced MAO B inhibitory activity in rat brain (p < 0.01). Fluoxetine inhibited both brain MAO A and B activities in rats (p < 0.01).Conclusion: The results suggest that CRLE produces significant antidepressant effect in rats, and therefore, may be useful for the treatment of depressed patients, but further studies are required to ascertain this.Keywords: Cyperus rotundus, Antidepressant, Tail suspension test, Forced swimming test, Monoamine oxidase, Fluoxetine

Anti-depressant effects of Gastrodia elata Blume and its compounds gastrodin and 4-hydroxybenzyl alcohol, via the monoaminergic system and neuronal cytoskeletal remodeling

Ethnopharmacology relevanceGastrodia elata Blume is a highly valuable traditional Chinese medicine used in the treatment of depression. However, compounds with antidepressant effects in water extracts of G. elata Bl. (WGE) have not been identified. The aims of this study were to determine the major antidepressant compound in WGE and to evaluate the antidepressant effects of WGE and its active compounds which involved the monoaminergic system and neuronal cytoskeletal remodeling. Materials and methodsGastrodin (GAS) and 4-hydroxybenzyl alcohol (HBA) in WGE, were analyzed with high-performance liquid chromatography (HPLC)-ultraviolet detection.The forced swimming test (FST) was used to induce depression-like symptoms in 9 weeks old male Sprague-Dawley rats. The open field test (OFT) was used to measure anxiety after WGE, GAS, and HBA treatments. The levels of monoamine such as serotonin (5-HT), dopamine (DA), and their metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using HPLC-electrochemical detection. Western blotting was used to examine the 5-HT1A receptor and the neuronal cytoskeleton remodeling-related proteins, Slit, dihydropyrimidinase-related protein 2 (DPYSL2, also called CRMP2), Ras homologous member A (RhoA), and profilin 1 (PFN1) in vivo. Slit1 expression was evaluated in Hs683 cell line after treated with WGE (0.5mg/mL), GAS (50, 100 and 100μM), and HBA (50, 100 and 100μM). ResultsOral administration of WGE (500mg/kg bw), GAS (100mg/kg bw), and HBA (100mg/kg bw) exhibited the anti-depressant effect by significantly reducing the immobility time in FST, monoamine metabolism including the 5-HT to 5-HIAA in the hippocampus and DA to DOPAC and HVA ratios in the frontal cortex, amygdala, and hippocampus. In the hippocampus, the expression of the neuronal cytoskeleton remodeling-related negative regulators Slit1 and RhoA were significantly down-regulated. In addition, the positive regulators CRMP2 and PFN1 were significantly up-regulated following GAS, HBA, and WGE treatments. Moreover, WGE, GAS, and HBA were directly down-regulated Slit1 expression in Hs683 cells. ConclusionWGE, GAS, and HBA exhibited potential anti-depressant effects in rats by decreasing monoamine metabolism and modulated cytoskeleton remodeling-related protein expression in the Slit-Robo pathway. These results suggest that WGE can be used as agent for depressive prevention.

Mesaton (phenylephrine) Potentiates the Antidepressant and Eliminates the Sedative Action of Amitriptyline in Rats

Single i.m. doses of amitriptyline (10–30 mg/kg) induced a mild antidepressant effect in rats, decreasing immobility in the Porsolt test by factors of no more than 1.3–1.7. These doses of amitriptyline had significant sedative effects, as they decreased horizontal activity in the open field by factors of 3–6 and reduced vertical activity by factors of 2–2.5. Combined single i.m. administration of a low dose of amitriptyline (3 mg/kg) or a high dose of amitriptyline (30 mg/kg) combined with Mesaton (phenylephrine) at a threshold dose of 0.02 mg/kg (ineffective when given alone), induced a maximum antidepressant effect, decreasing immobility in the Porsolt test by factors of 3 and 4.6 respectively, but had no sedative side effect in the open field. The mechanism of potentiation of the antidepressant effect and elimination of the sedative effect of amitriptyline appears to be based on stimulation of gastric mucosal afferents by Mesaton.

The influence and mechanisms of the volatile oil from Mgristica fragrans Houtt.on chronic unpredictable stress rats

Objective To observe antidepressant effect of the volatile oil of Myristica on rats and investigate the mechanisms of antidepressant effect. Methods 72 rats were assigned randomly into normal control group, model group, positive control group and groups of different doses of the volatile oil of Myristica.After all rats except normal control group were applied to unpredictable stimulation and different doses of drugs for 21 days, and unpredictable stimulation after 1 h of gavaging. Horizontal and vertical activities and sugar consumptions were tested after molding and oral administration. After the behavioral experiments, the brains of the rats were taken, and 5-hydroxy tryptamine(5-HT), dopamine, noradrenalin content and activity of monoamine oxidase were measured. Results Comparing with model group after gavaging, the high dose of the volatile oil of Myristica showed antidepressant effect in the rats, the situation of crossing(33.22±4.21) and rearing(9.56±1.74) was improved and sweet water consumption((60.81±14.48)%) of rats was increased, significantly comparison with model group(P 0.05). The high dose group could significantly increase the content of 5-HT((12.23±0.950)ng/ml), DA((179.11±15.20)pg/ml) and reduce the activity of monoamine oxidase((9.12±0.95)μg/ml) in rats' brain, and significant differences were showed compared with model group(P<0.01). Conclusion The volatile oil of Myristica has obvious antidepressant effect in rat chronic mild stress, its mechanism is related to increase the content of 5-HT and DA and reduce the activity of monoamine oxidase in rats' brain. Key words: The volatile oil of Myristica; Chronic stress-induced depression; Mechanism; Monoamine neurotransmitters

Medial Forebrain Bundle Deep Brain Stimulation has Symptom-specific Anti-depressant Effects in Rats and as Opposed to Ventromedial Prefrontal Cortex Stimulation Interacts With the Reward System.

In recent years, deep brain stimulation (DBS) has emerged as a promising treatment option for patients suffering from treatment-resistant depression (TRD). Several stimulation targets have successfully been tested in clinical settings, including the subgenual cingulum (Cg25) and the medial forebrain bundle (MFB). MFB-DBS has led to remarkable results, surpassing the effect of previous targets in terms of response latency and number of responders. However, the question remains as to which mechanisms underlie this difference. The aim of the present study was to thoroughly study the anti-depressant effect of MFB-DBS in the Flinders sensitive line (FSL) rat model of depression as well as to investigate whether MFB-DBS and Cg25-DBS operate through the same neurobiological circuits. FSL and control rats received bilateral high-frequency stimulation to the MFB at the level of the lateral hypothalamus, while being subjected to a variety of depression- and anxiety-related behavioral paradigms. To further compare the effects of MFB-DBS and Cg25-DBS on reward-related behavior, animals were stimulated in either the MFB or ventromedial prefrontal cortex (vmPFC, rodent analog to Cg25), while being tested in the intra-cranial self-stimulation paradigm. A marked symptom-specific anti-depressant effect of MFB-DBS was demonstrated. The ICSS-paradigm revealed that MFB-DBS, as opposed to vmPFC-DBS interacts with the reward system. Our data suggest that MFB-DBS and Cg25-DBS do not operate via the same neurobiological circuits. This differentiation might be of interest when selecting patients for either Cg25- or MFB-DBS.

Fluoxetine Potentiation of Omega-3 Fatty Acid Antidepressant Effect: Evaluating Pharmacokinetic and Brain Fatty Acid-Related Aspects in Rodents

We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10mg/kg day) or non-antidepressant (1mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies.

Antidepressant effects of an inverse agonist selective for α5 GABA-A receptors in the rat forced swim test

Abstract It has been shown in electrophysiological studies that the ligand L-655,708 possesses a binding selectivity and a moderate inverse agonist functional selectivity for α5-containing GABA-A receptors. The present study is aimed to investigate the antidepressant effects of the ligand L-655,708 in the forced swim test (FST) and its impact on locomotor activity in rats. The behavior of the animals was recorded with a digital camera, and the data were analyzed by one-way ANOVA, followed by Dunnett’s test. In FST, L-655,708 significantly decreased immobility time at a dose of 3 mg/kg after a single and repeated administration (p&lt;0.05), exerting acute and chronic antidepressant effects. However, it did not induce significant differences in the time of struggling behavior during FST. Furthermore, L-655,708 did not show a significant effect on locomotor activity (p&gt;0.05). These data suggest that negative modulation at GABA-A receptors containing the α5 subunit may produce antidepressant effects in rats. These effects were not confounded by locomotor influences.