Anxiety-like Behavior In Open Field Test Research Articles

Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression.

Postpartum depression (PPD) is another type of depression, including emotional fluctuation, fatigue, and anxiety. Based on the specific event like giving birth, it can be speculated that PPD might have its specific mechanism. Here, we confirmed that dexamethasone (DEX) administration during pregnancy (gestational days 16-18) induced depressive- and anxiety-like behaviors in dam (DEX-dam) after weaning period (3 weeks). DEX-dam showed anxiety-like behaviors in open-field test (OFT) and light-dark test (LD). In addition, DEX-dam exhibited depressive-like behaviors with the increased immobility time in forced swimming test (TST). Molecular analysis confirmed that microglia, rather than neurons, astrocytes, and oligodendrocytes, are involved in anxiety-/depressive-like behaviors. Notably, P2ry12, homeostatic gene, and purinoceptor, along with hyper-ramified form, were reduced in the hippocampus of DEX-dam. In addition, we found that IL-10 mRNA was reduced in lymph nodes without alteration of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Interestingly, anxiety-/depressive-like behaviors of DEX-dam were restored with the normalization of P2ry12 and IL-10 after 10 weeks postpartum without antidepressants. Our results propose that stress hormone elevation during pregnancy might be associated with PPD via microglial P2RY12 and peripheral IL-10.

Dynamics and immunomodulation of cognitive deficits and behavioral changes in non-severe experimental malaria.

Data recently reported by our group indicate that stimulation with a pool of immunogens capable of eliciting type 2 immune responses can restore the cognitive and behavioral dysfunctions recorded after a single episode of non-severe rodent malaria caused by Plasmodium berghei ANKA. Here we explored the hypothesis that isolated immunization with one of the type 2 immune response-inducing immunogens, the human diphtheria-tetanus (dT) vaccine, may revert damages associated with malaria. To investigate this possibility, we studied the dynamics of cognitive deficits and anxiety-like phenotype following non-severe experimental malaria and evaluated the effects of immunization with both dT and of a pool of type 2 immune stimuli in reversing these impairments. Locomotor activity and long-term memory deficits were assessed through the open field test (OFT) and novel object recognition task (NORT), while the anxiety-like phenotype was assessed by OFT and light/dark task (LDT). Our results indicate that poor performance in cognitive-behavioral tests can be detected as early as the 12th day after the end of antimalarial treatment with chloroquine and may persist for up to 155 days post infection. The single immunization strategy with the human dT vaccine showed promise in reversal of long-term memory deficits in NORT, and anxiety-like behavior in OFT and LDT.

Isolation, Antibacterial, Nematicidal and Anxiolytic Activities of Essential Oil from Cinnamomum longepaniculatum (Gamble) N. Chao ex H. W. Li Leaves

The utilization of natural product resources is significant for economic growth and health care. Herein, Cinnamomum longepaniculatum essential oil (CLEO) was isolated by microwave-assisted hydrodistillation (MAH). The composition of CLEO was determined by gas chromatography/mass spectrometry (GC/MS), and the antibacterial, nematicidal and anxiolytic activities of CLEO were evaluated. GC/MS results revealed that 33 compounds were identified, accounting for 99.87% of the total identified compounds. The major components of CLEO were monoterpenes, including β-myrcene (22.55%), eucalyptol (11.59%), α-pinene (11.56%), terpinen-4-ol (8.63%). Further research found that CLEO can inhibit the growth of Staphylococcus aureus (MIC 7.13 mg/mL, MBC 14.25 mg/mL), Escherichia coli (MIC 14.25 mg/mL, MBC 57 mg/mL), and Pseudomonas aeruginosa (MIC 14.25 mg/mL, MBC 28.50 mg/mL), the zone of inhibition were 17.49 ± 0.51 mm, 13.35 ± 0.27 mm and 15.15 ± 0.31 mm, respectively. CLEO could increase cell membrane permeability and make β-galactosidase, protein and other substances leak from the cell. Importantly, CLEO was first used to kill pine wood nematodes (PWN, Bursaphelenchus xylophilus). It was found that CLEO was toxic to B. xylophilus (LC50=30.81 mg/mL), and PWN treated with CLEO rapidly died and extended. Furthermore, CLEO was used in anxiolytic for the first time. CLEO inhalation can effectively relieve anxiety-like behaviors in open-field test (OFT) and elevated plus-maze test (EPT), and restore neurotransmitters (5-HT, NE, GABA) in brain tissue to normal levels. This study provides a strategy for the industrial production of CLEO and discovers its potential role in food transportation and preservation, forest pest control, and relief of emotional disorders such as anxiety and stress, which are beneficial to health care and economic development and provides a basis for broader application of CLEO.

The CA1 hippocampal serotonin alterations involved in anxiety-like behavior induced by sciatic nerve injury in rats

Several clinical and experimental studies reported the anxiety as one of the neuropathic pain comorbidities; however, the mechanisms involved in this comorbidity are incompletely cleared. The current study investigated the consequence of pain induced by peripheral neuropathy on the serotonin (5-HT) level of the CA1 region of the hippocampus, which is known as a potential reason, for anxiety associated with neuropathic pain. In this manner, 72 male rats were inconstantly subdivided into three experimental groups as follows: control, sham, and chronic constriction injury (CCI). Neuropathic pain was initiated by the CCI of the sciatic nerve, and then, mechanical allodynia, thermal hyperalgesia, and anxiety-like behavior were evaluated using the von Frey filaments, radiant heat, open field test (OFT), and elevated plus maze (EPM) respectively. To investigate the probable mechanisms, the in vivo extracellular levels of 5-HT were assessed by microdialysis and using reverse-phase high-pressure liquid chromatography (HPLC) in the CA1 region of hippocampus on days 16 and 30 post-CCI. Our data suggested that CCI caused anxiety-like behavior in OFT and EPM test. 5-HT concentration in the CA1 region of the hippocampus significantly (F=43.8, p=0.000) reduced in CCI rats, when the pain threshold was minimum. Nevertheless, these alterations reversed while the pain threshold innate increased. Neuropathic pain, initiated by constriction of the sciatic nerve can induce anxiety-like behavior in rats. This effect accompanies the reduction in 5-HT concentration in the CA1 region of the hippocampus. When the pain spontaneously alleviated, 5-HT level increased and anxiety-like behavior relieved.

The CA1 hippocampal serotonin level modulates anxiety-like behavior in neuropathic rats

Clinical and experimental studies reported that anxiety is the neuropathic pain comorbidity but the mechanisms involved in this comorbidity incompletely cleared. The current study investigated the consequence of pain induced by peripheral neuropathy on the serotonin (5HT) level of the CA1 region of the hippocampus as a potential reason for anxiety associated with neuropathic pain. In this manner, 25 male rats inconstantly were subdivided between three experimental groups (control, sham, chronic constriction injury). Neuropathic pain initiated by the chronic constriction injury of the sciatic nerve (CCI) then, mechanical allodynia, hyperalgesia and anxiety-like behavior evaluated using the Von Frey filaments, radiant heat, open field test (OFT) and elevated plus maze(EPM) respectively. To investigate the probable mechanisms, the in vivo extracellular levels of serotonin assessed by microdialysis and reverse-phase high-pressure liquid chromatography (HPLC) in the CA1 region of hippocampus on days 14, 21 and 28 post-CCI. Our data suggested that CCI caused anxiety-like behavior in OFT and EPM test. Serotonin concentration in the CA1 region of the hippocampus significantly (P < 0.001, F=10) reduced in CCI rats when the pain threshold was minimum. Nevertheless, these alterations reversed while the pain threshold innate increased. Neuropathic pain initiated by constriction of the sciatic nerve induces anxiety-like behavior in rats. This effect applies through the decrease in serotonin concentration in the CA1 region of the hippocampus. When pain spontaneously alleviated serotonin level increased and anxiety-like behavior relieved.

Gender-dependent regulation of anxiety-like behavior by δ subunit-containing GABAA receptor during postnatal development.

The δ subunit-containing GABAA receptor [GABAA(δ)R], which is exclusively situated in the extrasynaptic space, has considerable influence on emotion and behavior. Although the expression of this receptor experiences dramatic fluctuation during postnatal development, it remains unknown whether it regulates emotion in a development-dependent manner. Here, by using mice with genetic deletion of GABAA(δ)R (knockout) and their wild-type littermates, we examined the role of GABAA(δ)R in regulating anxiety-like behavior, as measured with open field test (OFT) and elevated plus maze during the transition from puberty to adulthood. We observed that for female mice, the knockout ones at puberty but not adulthood showed increased anxiety-like behavior in the OFT relative to their wild-type littermates. However, such increase was not observed in elevated plus maze. For male mice, no between-genotype differences were observed in both tests at the above two developmental stages. Our results suggest that GABAA(δ)R preferentially affects the anxiety-like behavior in OFT in a development-dependent manner, but only in female mice.

Effects of single parenthood on mothers' behavior, morphology, and endocrine function in the biparental California mouse

Motherhood is energetically costly for mammals and is associated with pronounced changes in mothers' physiology, morphology and behavior. In ~5% of mammals, fathers assist their mates with rearing offspring and can enhance offspring survival and development. Although these beneficial consequences of paternal care can be mediated by direct effects on offspring, they might also be mediated indirectly, through beneficial effects on mothers. We tested the hypothesis that fathers in the monogamous, biparental California mouse (Peromyscus californicus) reduce the burden of parental care on their mates, and therefore, that females rearing offspring with and without assistance from their mates will show differences in endocrinology, morphology and behavior, as well as in the survival and development of their pups. We found that pups' survival and development in the lab did not differ between those raised by a single mother and those reared by both mother and father. Single mothers spent more time in feeding behaviors than paired mothers. Both single and paired mothers had higher lean mass and/or lower fat mass and showed more anxiety-like behavior in open-field tests and tail-suspension tests, compared to non-breeding females. Single mothers had higher body-mass-corrected liver and heart masses, but lower ovarian and uterine masses, than paired mothers and/or non-breeding females. Mass of the gastrointestinal tract did not differ between single and paired mothers, but single mothers had heavier gastrointestinal tract compared to non-breeding females. Single motherhood also induced a flattened diel corticosterone rhythm and a blunted corticosterone response to stress, compared to non-breeding conditions. These findings suggest that the absence of a mate induces morphological and endocrine changes in mothers, which might result from increased energetic demands of pup care and could potentially help maintain normal survival and development of pups.

Centella asiatica prevents chronic unpredictable mild stress-induced behavioral changes in rats

Background: Depression is a psychological disorder which is associated with mood swings and cognitive deficits, and is ranked third among the leading causes of global health care burden. Chronic unpredictable mild stress (CUMS) has been shown to induce depression-like behaviors in rodents, which exhibit similarities to the human form of depression. Centella asiatica (CA) is an ancient medicinal plant which has neuroprotective potential. This work aimed to assess the protective role of CA on CUMS-induced rats.&#x0D; Methods: Thirty six rats randomly divided into six groups were used for the evaluation. The groups were as follows: 1, Unstressed + normal saline (control); 2, CUMS + normal saline (model); 3, CUMS + fluoxetine (10 mg/kg) standard antidepressant; 4-6, CUMS + CA (200, 400 &amp; 800 mg/kg). Nine different stressors (S) (S1: 24-h food deprivation, S2: 24- h water deprivation, S3: 5-min cold swimming (at 5◦C), S4: 12-h change of cage mate, S5: 1-min tail pinch (1 cm from the tip of the tail), S6: 12-h cage tilt (at 45◦), S7: 12-h overcrowding of cage, S8: 12-h wet bedding with 200 mL of water, and S9: 4-h physical restraint) were administered to the stressed groups with at least 2 stressors per day. The treatments lasted for 8 weeks, and the rats were evaluated through open field test (OFT) and elevated plus maze (EPM) for anxiety-like behavior, forced swimming test (FST) for depression-like behaviour, and T-maze spontaneous alternation for learning and memory. Furthermore, serum cortisol levels were also evaluated.&#x0D; Results: CUMS-induced rats showed anxiety-like behaviors in OFT and EPM tests, depression-like behavior in FST and cognitive deficits in T-maze test, as well as increased serum cortisol levels. Conversely, administration of CA (at 400 and 800 mg/kg doses) and fluoxetine (at 10 mg/kg dose) prevented the aberrant behavioral changes and also the changes in the serum cortisol levels. No significant differences of behaviors were observed between the groups of rats administered with CA (400 and 800 mg/kg) and those administered with fluoxetine (10 mg/kg), suggesting that the therapeutic potential of CA is comparable to that of fluoxetine.&#x0D; Conclusion: The data obtained showed that CA, at doses of 400 and 800 mg/kg, effectively reversed the anxiety and depression-like behaviors, amnesic behaviors, as well as serum cortisol levels in a CUMS-induced rat model of depression. This suggests that CA is a potential candidate for the development of future anti-depressants.&#x0D;

Tafa-2 plays an essential role in neuronal survival and neurobiological function in mice.

Tafa is a family of small secreted proteins with conserved cysteine residues and restricted expression in the brain. It is composed of five highly homologous genes referred to as Tafa-1 to -5. Among them, Tafa-2 is identified as one of the potential genes responsible for intellectual deficiency in a patient with mild mental retardation. To investigate the biological function of Tafa-2 in vivo, Tafa-2 knockout mice were generated. The mutant mice grew and developed normally but exhibited impairments in spatial learning and memory in Morris water maze test and impairments in short- and long-term memory in novel object recognition test, accompanied with increased level of anxiety-like behaviors in open-field test and elevated plus maze test, and decreased level of depression-like behaviors in forced-swim test and tail-suspension test. Further examinations revealed that Tafa-2 deficiency causes severe neuronal reduction and increased apoptosis in the brain of Tafa-2−/− mice via downregulation of PI3K/Akt and MAPK/Erk pathways. Conformably, the expression levels of CREB target genes including BDNF, c-fos and NF1, and CBP were found to be reduced in the brain of Tafa-2−/− mice. Taken together, our data indicate that Tafa-2 may function as a neurotrophic factor essential for neuronal survival and neurobiological functions.

Xiaochaihutang attenuates depressive/anxiety-like behaviors of social isolation-reared mice by regulating monoaminergic system, neurogenesis and BDNF expression

Ethnopharmacological relevanceXiaochaihutang (XCHT), as a classical herbal formula for the treatment of “Shaoyang syndrome” has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression. Materials and methodsMale C57 BL/6J mice (aged 4 weeks after weaning) were reared isolatedly for 8 weeks and XCHT (0.8, 2.3, 7.0g/kg) were given by gavage once a day. Forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated-plus maze test (EPM) and intruder-induced aggression test were used to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice after administration of XCHT for 6 weeks. HPLC-MS/MS was performed to quantify the levels of neurotransmitters in the hippocampus by in vivo microdialysis, while western immunoblotting was used to evaluate the action of XCHT on the synthesis, transport and degradation of monoamine neurotransmitters. Immunofluorescence was used to study the effects of XCHT on neurogenesis and neurotrophin expression, including Ki-67, DCX, BrdU and BDNF. ResultsOur results showed that administration of XCHT (0.8, 2.3 and 7.0g/kg) for 6 weeks significantly attenuated the increase in immobility time in TST and FST, improved the anxiety-like behaviors in OFT and EPM, and improved the aggressive behaviors of SI-reared mice. XCHT significantly elevated monoamine neurotransmitters levels and inhibited 5-HT turnover (5-HIAA/5-HT) in hippocampal microdialysates of SI-reared mice. In addition, we found XCHT enhanced monoamine neurotransmitter synthesis enzymes (TPH2 and TH) expressions, inhibited serotonin transporter (SERT) expression and decreased monoamine neurotransmitter degradation enzyme (MAOA) expression in the hippocampus of SI-reared mice for the first time. Moreover, XCHT significantly augmented hippocampal neurogenesis and BDNF expression in hippocampus of SI-reared mice. ConclusionsOur results showed for the first time that XCHT improved depressive/anxiety-like behaviors of SI-reared mice by regulating the monoaminergic system, neurogenesis and neurotrophin expression. The findings indicate that XCHT may have a therapeutic application for early-life stress model of depression and in turn provide further evidence supporting XCHT a novel potential antidepressant from a distinct perspective.