Decreased Immobility Time Research Articles

The effects of lipid lowering drugs on neuroinflammation in metabolic syndrome mice

People get used to high‐calorie and refined dishes diet and lack of physical exercises with rapid modern lifestyles change. Those bad habits contribute to the increasing prevalence of metabolic syndrome. The peripheral chronic inflammatory responses are related to the adipose tissue accumulation and hyperlipidemia in the metabolic syndrome patients. Depression is an important comorbidity with metabolic syndrome. The inflammatory cytokines secreted by activated inflammatory cells in peripheral tissue would induce central neural inflammation. Chronic brain inflammation may be linked to depression. We hypothesize that depression occurrence in metabolic syndrome patients is due to the peripheral and central neural inflammation. We evaluated whether fenofibrate or Statin could improve depression‐like behavior in metabolic syndrome mice. The metabolic syndrome mice were induced by high‐fat‐diet. The depression‐like behaviors in metabolic syndrome mice were analyzed by tail suspension test, open field test and sucrose preference test. After 4‐week treatment of fenofibrtae and Statin, the depression‐like behavior in mice were analyzed and then sacrificed. The expressions of inflammatory cytokines in the brain of mice were detected by RT‐PCR. The activation of macrophage and microglia were analyzed using IHC stain. The results showed that body weight, TG, TC in serum and adipose tissue weight of mice were increased after high‐fat‐diet fed. That confirmed metabolic syndrome was induced successfully in the mice. In behavior analysis, fenofibrate decreased immobility times of tail suspension, increased number of line crossing of open field test, and increase sucrose intake of sucrose preference test indicating that PPARα activation may improve depression‐like behavior. The data showed that fenofibrate could improve depression level in metabolic syndrome mice.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Applying ketamine to alleviate the PTSD-like effects by regulating the HCN1-related BDNF

BackgroundPost-traumatic stress disorder (PTSD) is commonly associated with concurrent anxiety and depression symptoms, and reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF) which promotes the proliferation and survival of neurons. The hyperpolarization-activated cyclic nucleotide-gated channel 1(HCN1) could be inhibited by the ketamine, a drug to alleviate depression and anxiety, and regulated the BDNF expression, however, the effects of ketamine in alleviating PTSD symptoms by regulating the HCN1-related BDNF have been poorly perceived. MethodsIn the present study, the effects of ketamine were examined on the PTSD-like effects in a rat model of PTSD induced by SPS&S procedure. After the SPS&S procedure and model testing, PTSD rats were subjected to behavioral testing and biochemical assessments, followed by single treatment with certain doses of ketamine (5, 10, 15 and 20 mg/kg IP). ResultsThe results showed that the SPS&S procedure induced severe PTSD-like behaviors, with lower levels of BDNF protein levels and higher level of the HCN1 protein in the prefrontal cortex (PFC). These were reversed by a single administration of ketamine. The ketamine with dose of 15 mg/kg significantly increased locomotor behavior in the open field test, aggrandized exploratory behavior in the elevated plus maze test, and decreased immobility time spent in the forced swim test. Meanwhile, ketamine with dose of 15 mg/kg could increase the BDNF protein level, while down-regulate the expression of the HCN1. Eventually, there was a negative correlation between the level of BDNF and HCN1 in the PFC. ConclusionKetamine affects the HCN1-related BDNF signaling pathways to alleviate PTSD-like effects in rat.

Histamine-deficient mice do not respond to the antidepressant-like effects of oleoylethanolamide

It has been suggested that the bioactive lipid mediator oleoylethanolamide (OEA), a potent agonist of the peroxisome proliferator-activated receptor-alpha (PPAR-α) possesses anti-depressant-like effects in several preclinical models. We recently demonstrated that several of OEA's behavioural actions require the integrity of the brain histaminergic system, and that an intact histaminergic neurotransmission is specifically required for selective serotonin re-uptake inhibitors to exert their anti-depressant-like effect. The purpose of our study was to test if OEA requires the integrity of the histaminergic neurotransmission to exert its antidepressant-like effects. Immobility time in the tail suspension test was measured to assess OEA's potential (10 mg/kg i.p.) as an antidepressant drug in histidine decarboxylase null (HDC−/-) mice and HDC+/+ littermates, as well as in PPAR-α+/+ and PPAR-α−/− mice. CREB phosphorylation was evaluated using Western blot analysis in hippocampal and cortical homogenates, as pCREB is considered partially responsible for the efficacy of antidepressants. Serotonin release from ventral hippocampi of HDC+/+ and HDC−/- mice was measured with in-vivo microdialysis, following OEA administration. OEA decreased immobility time and increased brain pCREB levels in HDC+/+ mice, whereas it was ineffective in HDC−/- mice. Comparable results were obtained in PPAR-α+/+ and PPAR-α−/− mice. Microdialysis revealed a dysregulation of serotonin release induced by OEA in HDC−/- mice.Our observations corroborate our hypothesis that brain histamine and signals transmitted by OEA interact to elaborate appropriate behaviours and may be the basis for the efficacy of OEA as an antidepressant-like compound.

DEC2 modulates orexin expression and regulates sleep

Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene (BHLHE41) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin, also known as hypocretin (Hcrt), gene expression is increased in the mouse model expressing the mutant hDEC2 transgene (hDEC2-P384R). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal. In cell culture, DEC2 suppressed prepro-orexin promoter-luc (ore-luc) expression through cis-acting E-box elements. The mutant DEC2 has less repressor activity than WT-DEC2, resulting in increased orexin expression. DEC2-binding affinity for the prepro-orexin gene promoter is decreased by the P384R mutation, likely due to weakened interaction with other transcription factors. In vivo, the decreased immobility time of the mutant transgenic mice is attenuated by an orexin receptor antagonist. Our results suggested that DEC2 regulates sleep/wake duration, at least in part, by modulating the neuropeptide hormone orexin.

Thymoquinone and fluoxetine alleviate depression via attenuating oxidative damage and inflammatory markers in type-2 diabetic rats

The study was designed to find out the effect of thymoquinone (TQ) alone and combination of TQ + fluoxetine in depression of type-2 diabetic rats. Glucose level was significantly decreased in TQ alone treated group, whereas no significant change was recorded when TQ was combined with fluoxetine. Administration of TQ alone and combination of TQ and fluoxetine significantly decreased immobility time, increased latency to immobility and increased locomotor activity. Treatment with TQ alone significantly decreased level of TBARS, increased GSH and restored the activities of antioxidant enzymes (GPx, GR & CAT). However, TQ and fluoxetine combination reduced TBARS level, increased GSH content but no change in the antioxidant enzymes activities. Inflammatory markers (IL-1β, IL-6 & TNF-α) levels were significantly reduced after the administration of TQ alone and TQ + fluoxetine. The study suggests that combination of TQ and fluoxetine can be used to control depression in type-2 diabetes mellitus.

Study on antidepressant activity of chiisanoside in mice

The antidepressant-like effect of chiisanoside from the leaves of Acanthopanax sessiliflorus was evaluated by using mice models of depression, forced swim test (FST) and tail suspension test (TST). The results showed that treatment with chiisanoside at dose of 5.0 mg/kg significantly decreased immobility time in the FST and TST. Pretreatment with haloperidol (a non-selective D2 receptor antagonist), bicuculline (a competitive GABA antagonist) and N-methyl-D-aspartic acid (NMDA, an agonist at the glutamate site) effectively reversed the antidepressant-like effect of chiisanoside (5.0 mg/kg). Moreover, chiisanoside treatment did not change the locomotor activity. And chiisanoside (5.0 mg/kg) also effectively increased the dopamine (DA) and γ-aminobutyric acid (GABA) levels in mice brains exposed to the FST and TST in the co-treatment groups. Then we designed lipopolysaccharide (LPS)-induced antidepressant behavioral experiment, the results showed that LPS significantly increased immobility duration in the TST and FST. Chiisanoside administration could effectively reduce serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels; at the same time, the changes of related indexes of oxidative stress are improved, such as superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover, chiisanoside effectively down-regulated brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) and nuclear factor-κB (NF-κB) in hippocampal. In conclusion, chiisanoside displayed significant antidepressant-like effect, which was probably related to the DAergic, GABAergic and glutamatergic systems. And the mechanism of anti-depressant effect of chiisanoside might be via the alterations of animal behaviors, hippocampus inflammation, oxidative stress and neurotrophy, which might be attributed by the BDNF/TrkB/NF-κB pathway.

Antidepressive effects of Gami-Shinkiwhanin immobilization stressed aging mice

Background/Objectives: This study investigated the antidepressive effects of Gami-Shinkiwhan (GS) in immobilization stressed aging mice. Methods/Statistical analysis: 24-month-old ICR mice were used in this study. The groups were consistedof a control group, depressed group (DS group), and Gami-Shinkiwhan-treated group (GS group). DS and GS groups were exposed to immobilization stress for 10 weeks; GS was treated at a dose of 0.56 g/kg/day. Depression was assessed using the tail suspension test (TST) and immunohistochemical staining of hippocampal tissue. Findings: The mice from the GS group exhibited decreased immobility time in the TST, compared to the immobility time of the mice from the DS group. Immunohistochemical analysis revealed that the levels of serotonin and SHH significantly increased, while the levels of caspase-3 and HDAC3 significantly decreased in the GS group, compared to the levels in the DS group. Improvements/Applications: Taken together, results indicate that GS alleviates depression in aging mice by increasing the levels of serotonin and SHH, and decreasing the levels of caspase-3 and HDAC3 in the hippocampus.

Antidepressant-Like Effects of Vaccinium bracteatum in Chronic Restraint Stress Mice: Functional Actions and Mechanism Explorations.

The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT[Formula: see text] receptor by inhibiting 5-HT-induced intracellular Ca[Formula: see text] and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT[Formula: see text] receptor.

Surface modification of PGP for a neutrophil–nanoparticle co-vehicle to enhance the anti-depressant effect of baicalein

Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala (BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized (OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.

A new piperazine derivative: 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one with antioxidant and central activity.

In the scope of a research program aimed at developing new drugs for the treatment of central nervous system diseases, we describe herein the synthesis and pharmacological evaluation of 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one (LQFM180). This compound showed antioxidant activity in two models, electroanalytical assays, and DPPH activity. Moreover, in behavioral tests as the open field test LQFM180 (9.4, 18.8, and 37.6mg/kg, per oral (p.o.)), we detected anxiolytic-like activity. In the sodium pentobarbital-induced sleep test, LQFM180, in all doses, decreased the latency to sleep and increased sleep duration, indicating central depressant activity; moreover, in the chimney test, LQFM180 did not alter motor activity. LQFM180 (18.8mg/kg, p.o.) increased the time and number of entries on open arms in the elevated plus maze test, suggesting anxiolytic-like activity, which was reversed by NAN-190 and p-chlorophenylalanine, indicating a role of the serotonergic pathway on this effect. In the forced swimming test, LFQM180 (18.8mg/kg, p.o.) decreased immobility time, suggesting antidepressant-like activity, which was reversed by monoaminergic antagonists, indicating a role for the serotonergic, noradrenergic, and dopaminergic pathways. Competition binding assays showed that LQFM180 was able to bind to the α1B, 5-HT1A, and D2 receptors, however, within the low micromolar range. We conclude that LQFM180 should be considered as a scaffold for drug candidate development.

Deletion of GIRK2 subunit containing GIRK channels of neurons expressing dopamine transporter decrease immobility time on forced swimming in mice.

We previously reported that non-narcotic antitussives possessing inhibitory actions on G protein-coupled inwardly rectifying potassium (GIRK) channels have antidepressant-like effects in the forced swimming test in normal and adrenocoticotropic hormone (ACTH) treated rats. Furthermore, the antidepressant-like effects of the antitussives such as tipepidine were blocked by dopamine D1 receptor antagonist, and inhibitory actions on GIRK channels of dopamine neurons may be involved in the antidepressant-like effects of tipepidine. In this study, we generated GIRK2DATKO mice with Girk2/Kcnj6 conditional deletion and assessed depression-related behavior of the mice. The Cre/loxP system was used to selectively delete GIRK2 subunit containing GIRK channels in the neurons expressing dopamine transporter. First, deletion of GIRK2 subunits in the ventral tegmental area (VTA) neurons expressing dopamine transporters was confirmed by hisitochemically and electrophysiologically. In the mice, a significant decrease in the immobility time of forced swimming test was observed. Locomotor activity of the mice was not changed compared to that of GIRK2floxed mice, when tested in the open field. These results suggest that the antidepressant-like effect of antitussives such as tipepidine may be caused partly through the inhibitory actions on GIRK channels in the dopamine neurons.

Antidepressant-like effect of zileuton is accompanied by hippocampal neuroinflammation reduction and CREB/BDNF upregulation in lipopolysaccharide-challenged mice

BackgroundRecent studies demonstrated beneficial effects of zileuton, a 5-lipoxygenase (5LO) inhibitor, on some brain diseases in animal models, but the role of zileuton in the depression remains unknown. MethodsWe investigated the effects of zileuton on depressive behaviors using tail suspension test (TST), forced swimming test (FST) and novelty-suppressed feeding test (NSFT) in mice injected with lipopolysaccharide (LPS). The 5LO level, activation of microglia, NF-κB p65, TNF-α, IL-1β, brain-derived neurotrophic factor (BDNF), and c-AMP response element-binding protein (CREB) were determined in the mouse hippocampus. ResultsWe firstly found that the expression of hippocampal 5LO was gradually increased over LPS exposure and was reversed by fluoxetine administration. Zileuton significantly suppressed LPS-induced depressive behaviors, evidenced by the decreases in immobility time in TST and FST, as well as the latency to feed in NSFT. This treatment pronouncedly alleviated LPS-induced neuroinflammatory response, characterized by decreased 5LO, suppressed activation of microglia, decreased NF-κB p65, TNF-α and IL-1β, and significantly increased the ratio of p-CREB/CREB or mBDNF/proBDNF in the hippocampus of the LPS-challenged mice. ConclusionsZileuton abrogates LPS-induced depressive-like behaviors and neuroinflammation, and enhances CREB/BDNF signaling in the hippocampus, suggesting that zileuton could have potential therapeutic value for depression.

Chronic treatment with caffeine and its withdrawal modify the antidepressant-like activity of selective serotonin reuptake inhibitors in the forced swim and tail suspension tests in mice. Effects on Comt, Slc6a15 and Adora1 gene expression

Recent preclinical and clinical data suggest that low dose of caffeine enhances the effects of common antidepressants. Here we investigated the effects of chronic administration of caffeine (5mg/kg, twice daily for 14days) and its withdrawal on day 15th on the activity of per se ineffective doses of fluoxetine (5mg/kg) and escitalopram (2mg/kg) given on day 15th. We found decreased immobility time in the forced swim and tail suspension tests in mice in which caffeine was administered simultaneously with antidepressants on day 15th following a 14-day caffeine treatment and no alterations in the spontaneous locomotor activity. A decrease in the level of escitalopram and an increase in the level of caffeine in serum were observed after concomitant administration of these compounds, while the joint administration of caffeine and fluoxetine was not associated with changes in their levels in serum or brain. Caffeine withdrawal caused a decrease in Adora1 mRNA level in the cerebral cortex (Cx). Administration of escitalopram or fluoxetine followed by caffeine withdrawal caused an increase in this gene expression, whereas administration of escitalopram, but not fluoxetine, on day 15th together with caffeine caused a decrease in Adora1 mRNA level in the Cx. Furthermore, antidepressant-like activity observed after joint administration of the tested drugs with caffeine was associated with decreased Slc6a15 mRNA level in the Cx. The results show that withdrawal of caffeine after its chronic intake may change activity of antidepressants with concomitant alterations within monoamine, adenosine and glutamate systems.

Study of antidepressant effects of grape seed oil in male mice using tail suspension and forced swim tests

<p class="Abstract">The aim of this study was to investigate the antidepressant effects of grape seed oil in male mice (n=60) using tail suspension and forced swim tests. Mice were divided to six groups of 10 in each group. Group I: Intraperitoneally receiving normal saline; Group II: Received normal saline & stress; Group III-V: Injected (i.p.) with different (60, 120, and 240 mg/kg) doses of grape seed oil; and Group VI: Received fluoxetine (10 mg/kg). Grape seed oil in 60 mg/kg significantly decreased immobility time in tail suspension and forced swim tests under chronic unpredictable stress compared to groups under chronic stress receiving normal saline and grape seed oil (120 and 240 mg/kg). Grape seed oil (60 mg/kg) significantly improved the motor balance in mice under chronic stress. It had no significant effect on serum corticosterone level. Grape seed oil can improve depression symptoms in mice.</p><p><strong>Video Clip of Methodology</strong>:</p><p>0 min 14 sec <a href="https://youtube.com/v/7JgyR4mTUOw">Full Screen</a> <a href="https://youtube.com/watch?v=7JgyR4mTUOw">Alternate</a></p>

Senegenin exerts anti-depression effect in mice induced by chronic un-predictable mild stress via inhibition of NF-κB regulating NLRP3 signal pathway

Depressive disorder is a kind of affective disturbance disease. Emerging evidence has suggested that inflammation may contribute to the pathologic process of depressive disorder. Senegenin (SEN), a major bioactive constituent in Polygala tenuifolia Willd, has much bioactivity including anti-inflammatory and neuroprotection effects. However, the mechanism of its anti-depressant effect in mice remains unknown. This study aimed to explore the anti-depressant effects of SEN on behavioral changes and inflammatory responses in mice induced by chronic un-predictable mild stress (CUMS). SEN treatment remarkably ameliorated CUMS-induced behavioral abnormalities, such as improving locomotor activity, decreasing immobility time in Tail suspension test (TST) and Forced swimming test (FST), and increasing sucrose intake in Sucrose preference test (SPT). Additionally, SEN improve protein levels of Brain-derived neurotrophic factor (BDNF) and Neurotrophin-3 (NT-3) expression.In response to stress, p65 was activated to promote production of pro-IL-1β, and then cleaved to mature IL-1β by NOD-like receptor protein 3 (NLRP3) inflammasome pathway in hippocampus of CUMS mice. After SEN treatment, protein activation related to NLRP3 inflammasome pathway was down-regulated, which inhibited IL-1β secretion. These results demonstrate that SEN plays an important role in treatment CUMS-induced depression in mice, possibly via suppression of pathway activation associated with NLRP3 inflammasome.

The antidepressant-like activity of ellagic acid and its effect on hippocampal brain derived neurotrophic factor levels in mouse depression models

The aim of present study was to evaluate the antidepressant-like activity of ellagic acid (EA) in mice-forced swim test (FST) and tail suspension test (TST) and the possible role of brain-derived neurotrophic factor (BDNF) in EA’s antidepressant-like effect. We found that EA and sertraline did not affect the spontaneous locomotor activity of mice. EA produced statistically significant decrease in immobility time as compared to vehicle group in TST. EA at 1 and 5 mg/kg doses did not produce any significant effect in immobility time as compared to vehicle group in FST. But EA produced significantly reduced immobility time at 2.5 mg/kg dose. EA treatment increased hippocampal BDNF level. This study demonstrates that EA is able to produce antidepressant-like effect in both TST and FST in mice. Moreover, the antidepressant-like effects of EA seems to be mediated by increased BDNF level in mice hippocampus.

Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression.

The FGFR1-5-HT1A heteroreceptor complexes are involved in neuroplasticity in the rat hippocampus and in the mesencephalic raphe 5-HT nerve cells. There exists a 5-HT1A protomer enhancement of FGFR1 protomer signaling. Acute and 10 day treatment with intracerebroventricular (i.c.v.) FGF-2 and the 5-HT1A agonist 8-OH-DPAT produced enhanced antidepressant effects in the forced swim test (FST). We studied in the current work the disturbances in the FGFR1-5-HT1A heterocomplexes in a genetic rat model of depression, the Flinders sensitive line (FSL) rats of Sprague-Dawley (SD) origin, by means of neurochemical, neurophysiological and behavioral techniques. In control SD rats, the FGFR1 agonist SUN11602 and FGF2 produced a significant reduction of G protein-coupled inwardly rectifying K+ channel (GIRK) currents induced by 8-OH-DPAT in the CA1 area of the hippocampus. In FSL rats, only i.c.v. 8-OH-DPAT alone treatment produced a significant reduction in the immobility time. The combined i.c.v. treatment (FGF2 + 8-OH-DPAT) in FSL rats did not cause a significant decrease in immobility time in the FST. However, in the SD rats this combined treatment produced a significant reduction. Furthermore, in the FSL rat a significant increase in the density of FGFR1-5-HT1A proximity ligation assay (PLA) positive clusters was only found after i.c.v. 8-OH-DPAT treatment alone in the CA2 and CA3 areas. In the SD rat a significant increase in the density of specific PLA clusters was only observed in the CA2 area of the i.c.v. combined treatment (FGF2 + 8-OH-DPAT) group. No treatment led to significant changes in the PLA clusters of the dorsal raphe in the FSL rat. However, significant changes in the density of specific PLA clusters were only found in the dorsal raphe of SD rats after combined treatment and treatment with 8-OH-DPAT alone. The results indicate that in FSL rats compared with SD rats alterations may develop in the ability of 8-OH-DPAT and combined FGFR1 and 5-HT1A agonist treatment to increase the density of FGFR1-5-HT1A heteroreceptor complexes of the dorsal raphe. It is proposed that such deficits in FSL rats may possibly reflect a failure of the combined agonist treatment to uncouple the 5-HT1A autoreceptors from the GIRK channels. This may contribute to the failure of producing antidepressant-like effects in the FSL rat by combined agonist treatment as seen in the SD rat. The antidepressant-like effects seen with the 5-HT1A agonist alone treatment in FSL but not in SD rats may instead involve significant increases in the FGFR1-5-HT1A complexes of the CA2 and CA3 areas of the hippocampus.

Chronic trans-astaxanthin treatment exerts antihyperalgesic effect and corrects co-morbid depressive like behaviors in mice with chronic pain.

Patients suffering from chronic neuropathic pain are at high risk of co-morbid depression, which burdens healthcare. Trans-astaxanthin has been shown in our previous studies to exert antidepressant-like effect. This work aimed to investigate the effects of trans-astaxanthin on pain-related depressive-like behaviors in mice and explored the mechanism(s). Chronic constriction injury (CCI) model was used in this research. Chronic pain was evaluated by thermal hyperalgesia in Hargreaves test and mechanical allodynia in von Frey test, depressive-like behaviors were evaluated by immobility time in forced swim test and tail suspension test. Chronic trans-astaxanthin treatment ameliorated mechanical allodynia and thermal hyperalgesia, as well as decreasing immobility time in forced swim test and tail suspension test in CCI mice, and these actions were abolished by co-treatment with P-Chlorophenylalanine (PCPA). Subsequent study indicated that indoleamine 2,3-dioxygenase (IDO) expression increased after CCI surgery in hippocampus and spinal cord, accompanied by increase of kynurenine (KYN)/tryptophan (TRY) ratio, decrease of serotonin (5-HT)/TRY ratio and decrease of 5-HT/5-HIAA ratio. The above results affected by CCI surgery were reversed by trans-astaxanthin treatment. Moreover, trans-astaxanthin at 80mg/kg was demonstrated to effectively antagonize IL-1β, IL-6 and TNF-α expression in hippocampus and spinal cord of CCI mice. Taken together, chronic trans-astaxanthin administration exerts therapeutic effects on thermal hyperalgesia and co-morbid depressive-like behaviors in CCI mice. These effects of trans-astaxanthin involves the serotonergic system, and also may be owing to its potent anti-inflammatory property.

POTENTIAL ANTIDEPRESSANT EFFECT OF OLIVE OIL IN ADULT MALE RATS EXPOSED TO RESTRAINT STRESS: ROLE OF BRAIN STEM SEROTONIN

Background: Olive oil (OO) has neuroprotective effects and is inversely associated with depression risk. However, the role of neurotransmitter systems in the pathophysiology of depression is still unclear. Objectives: In the present study, the antidepressant effect of olive oil and the underlying neurochemical mechanism were investigated. Materials and methods: Twenty eight male albino rats were allocated into four equal groups: Control group, OO-supplemented group (OO was given in a daily dose of 300 μl/kg by gavage 5 days a week for 2 consecutive weeks, restraint stress (RS) group, and OO+RS group. Forced swim test was performed and immobility time was measured. Serotonin, malondialdehyde (MDA) and glutathione peroxidase (GPx) in the brain stem homogenate, and cortisol level in the serum were measured. Results: Restraint stress group showed significant decrease in immobility time during forced swimming test, along with significant increase in serum cortisol, serotonin and MDA, and significant decrease in GPx. In the OO+RS group, immobility time was significantly reduced compared to restraint stress group and compared to control group. Cortisol, serotonin and MDA decreased and GPx increased. Conclusion: Olive oil has antidepressant potential which could be mediated via its antioxidant not its neurochemical effects.

Methyl Jasmonate Ameliorates Unpredictable Chronic Mild Stress‐Induced Behavioral and Biochemical Alterations in Mouse Brain

Preclinical Research The effects of methyl jasmonate (MJ; 5, 10, 20 mg/kg, i.p), a natural product widely used for the relief of stress, depression, and exhaustion on unpredictable chronic mild stress (UCMS)-induced depression-like behaviors in mice was assessed and compared to those of imipramine (IMP; 10 mg/kg, i.p). MJ and IMP were given 30 min before exposure to UCMS with the procedure repeated daily for 2 weeks; 24 h after the stress session, the tail suspension test (TST) and sucrose preference test were assessed. MJ decreased immobility time in the TST and reversed impaired intake of sucrose relative to the stressed control suggesting antidepressant-like activity. MJ also reduced UCMS-induced increases in corticosterone and MDA (malondialdehyde) levels and attenuated UCMS-induced decreases in GSH and TNF-α levels and SOD activity. These findings suggest that MJ attenuated UCMS-induced depressive-like behaviors through decreased levels of corticosterone and decreasing oxidative stress and neuroinflammation in mouse brain.Drug Dev Res 78 : 381-389, 2017. © 2017 Wiley Periodicals, Inc.