scholarly journals GluD1 knockout mice with a pure C57BL/6N background show impaired fear memory, social interaction, and enhanced depressive-like behavior

2019 ◽  
Author(s):  
Chihiro Nakamoto ◽  
Meiko Kawamura ◽  
Ena Nakatsukasa ◽  
Rie Natsume ◽  
Keizo Takao ◽  
...  

AbstractThe GluD1 gene is associated with susceptibility for schizophrenia, autism, depression, and bipolar disorder. However, the function of GluD1 and how it is involved in these conditions remain elusive. In this study, we generated a GluD1-knockout (GluD1-KO) mouse line with a pure C57BL/6N genetic background and performed several behavioral analyses. Compared to a control group, GluD1-KO mice showed no significant anxiety-related behavioral differences, evaluated using behavior in an open field, elevated plus maze, a light-dark transition test, the resident-intruder test of aggression and sensorimotor gating evaluated by the prepulse inhibition test. However, GluD1-KO mice showed (1) hyper locomotor activity in the open field, (2) decreased sociability and social novelty preference in the three-chambered social interaction test, (3) impaired memory in contextual, but not cued fear conditioning tests, and (4) enhanced depressive-like behavior in a forced swim test. Pharmacological studies revealed that enhanced depressive-like behavior in GluD1-KO mice was restored by the serotonin reuptake inhibitors imipramine and fluoxetine, but not the norepinephrine transporter inhibitor desipramine. In addition, biochemical analysis revealed no significant difference in protein expression levels, such as other glutamate receptors in the synaptosome and postsynaptic densities prepared from the frontal cortex and the hippocampus. These results suggest that GluD1 plays critical roles in fear memory, sociability, and depressive-like behavior.

Author(s):  
Jessica MacGregor

gene in humans have been shown to predict non-responsiveness to antidepressant drugs; suggesting that FGF2 is required for antidepressants to work. In this study, we hypothesized that antidepressants will not work in rodents that lack the FGF2 gene. Hence, we tested antidepressant treatment in transgenic mice that had the FGF2 gene knocked out. Chronic unpredictable stress (CUS) has been used for several decades to produce a reliable depressive and anxious phenotype in mice. This study followed a CUS paradigm and used fluoxetine (Prozac) as antidepressant treatment. Mice received daily fluoxetine administration beginning on week three of CUS and continued until the end of week five to provide an antidepressant effect and reverse the effects of stress. To test for levels of anxiety and depression, a battery of behavioral tests was conducted which began from the least stressful (i.e. sucrose preference test, open field maze, elevated plus maze) to the most stressful test (forced swim test) to prevent testing carry-over effects. AnyMaze software was used to measure behavior in the open field and elevated plus mazes by recording the amount of time each mouse spent in certain parts of the maze. Future studies will examine brain changes associated with FGF2 gene deletion – particularly in astrocyte cells – which might be necessary for successful antidepressant action. Hopefully, this will elucidate novel therapeutic targets for antidepressant and anti-anxiety medication. 


Author(s):  
Puja Jha ◽  
Seema Bhalerao ◽  
Mrunal Dhole

Background: Anxiety affects around 7.3% of the total population worldwide. Benzodiazepines are preferred anxiolytic agents and are still frequently used in spite of the side effect profile including muscle relaxation, memory disturbances, sedation, physical dependence. Arnica montana, a traditional herb is known to possess significant anxiolytic effect at the dose of 100mg/kg. In this study, Arnica montana has been compared for the first time with alprazolam, a most commonly used anxiolytic drug.Methods: Forced swim test was used to induce anxiety. Anxiolytic action of study drugs which were given orally, was evaluated using Open field test (OFT) in healthy wistar rats of either sex. Behavior of rats, locomotion and number of squares crossed was recorded. Rats were divided into four groups with eight rats in each group. Study groups were Group I Control; Group II Alprazolam 0.08mg/kg; Group III Arnica montana extract (AME) 100mg/kg; Group IV AME + Alprazolam group 100mg/kg+0.08mg/kg. Statistical analysis was done using ANOVA followed by Tukey’s test (p<0.05).Results: Increase in frequency of rearing was significant (p<0.05) in AME group and highly significant (p<0.001) in Alprazolam and combination group in comparison to control. Decrease in frequency of grooming was highly significant (p<0.001) in Alprazolam and combination group. AME also showed significant (p<0.05) decrease in grooming activity.Conclusions: Arnica montana extract showed anxiolytic activity and can be used as an add on drug after further studies and validation in the treatment of anxiety disorders.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jieqiong Wang ◽  
Chunhong Song ◽  
Dongmei Gao ◽  
Sheng Wei ◽  
Wenjun Sun ◽  
...  

This study is to investigate the effect of Paeonia lactiflora extract on PMS anxiety and on expression of estrogen receptor β (ERβ), tryptophan hydroxylase-2 (TPH2), and serotonin transporter (SERT) in the premenstrual syndrome (PMS) anxiety model rats. The vaginal smear and open field test were used to screen rats in nonreception phase of estrus cycle with similar macroscopic behaviors and regular estrus cycle. PMS anxiety model rats were prepared by electrical stimulation. RT-PCR and immunofluorescence were used to measure the expression of ERβ, TPH2, and SERT. Compared with normal rats, the total distance in the open field test of the model rats was significantly increased (P<0.05). The model rats showed nervous alertness, irritability, and sensitivity to external stimuli. After treatment with the Paeonia lactiflora extract, the total distance of rats was significantly reduced (P<0.05). In reception stage, there was no significant difference in the mRNA and protein expression of ERβ, TPH2, and SERT. In nonreception stage, the expression of ERβ and TPH2 in the model group was significantly decreased (P<0.05) as compared with the control group, but not SERT. Abnormal changes of the above indicators were reversed after the administration of the Paeonia lactiflora extract. In conclusion, Paeonia lactiflora extract can increase the expression of ERβ and TPH2 and decrease SERT in PMS model rats, which may be one of the mechanisms underlying the effect of Paeonia lactiflora extract on PMS.


2020 ◽  
Vol 21 (8) ◽  
pp. 2837 ◽  
Author(s):  
Yu-Nung Lin ◽  
Gilbert Audira ◽  
Nemi Malhotra ◽  
Nguyen Thi Ngoc Anh ◽  
Petrus Siregar ◽  
...  

Lysophosphatidic acid (LPA) is a small lysophospholipid molecule that activates multiple cellular functions through pathways with G-protein-coupled receptors. So far, six LPA receptors (LPAR1 to LPAR6) have been discovered and each one of them can connect to the downstream cell message-transmitting network. A previous study demonstrated that LPA receptors found in blood-producing stem cells can enhance erythropoietic processes through the activation of LPAR3. In the current study, newly discovered functions of LPAR3 were identified through extensive behavioral tests in lpar3 knockout (KO) zebrafish. It was found that the adult lpar3 KO zebrafish display an abnormal movement orientation and altered exploratory behavior compared to that of the control group in the three-dimensional locomotor and novel tank tests, respectively. Furthermore, consistent with those results, in the circadian rhythm locomotor activity test, the lpar3 KO zebrafish showed a lower level of angular velocity and average speed during the light cycles, indicating an hyperactivity-like behavior. In addition, the mutant fish also exhibited considerably higher locomotor activity during the dark cycle. Supporting those findings, this phenomenon was also displayed in the lpar3 KO zebrafish larvae. Furthermore, several important behavior alterations were also observed in the adult lpar3 KO fish, including a lower degree of aggression, less interest in conspecific social interaction, and looser shoal formation. However, there was no significant difference regarding the predator avoidance behavior between the mutant and the control fish. In addition, lpar3 KO zebrafish displayed memory deficiency in the passive avoidance test. These in vivo results support for the first time that the lpar3 gene plays a novel role in modulating behaviors of anxiety, aggression, social interaction, circadian rhythm locomotor activity, and memory retention in zebrafish.


2013 ◽  
Vol 16 (5) ◽  
pp. 1059-1070 ◽  
Author(s):  
Marco Bortolato ◽  
Megan M. Yardley ◽  
Sheraz Khoja ◽  
Sean C. Godar ◽  
Liana Asatryan ◽  
...  

Abstract Purinergic ionotropic P2X receptors are a family of cation-permeable channels that bind extracellular adenosine 5′-triphosphate. In particular, convergent lines of evidence have recently highlighted P2X4 receptors as a potentially critical target in the regulation of multiple nervous and behavioural functions, including pain, neuroendocrine regulation and hippocampal plasticity. Nevertheless, the role of the P2X4 receptor in behavioural organization remains poorly investigated. To study the effects of P2X4 activation, we tested the acute effects of its potent positive allosteric modulator ivermectin (IVM, 2.5–10 mg/kg i.p.) on a broad set of paradigms capturing complementary aspects of perceptual, emotional and cognitive regulation in mice. In a novel open field, IVM did not induce significant changes in locomotor activity, but increased the time spent in the peripheral zone. In contrast, IVM produced anxiolytic-like effects in the elevated plus maze and marble burying tasks, as well as depression-like behaviours in the tail-suspension and forced swim tests. The agent induced no significant behavioural changes in the conditioned place preference test and in the novel object recognition task. Finally, the drug induced a dose-dependent decrease in sensorimotor gating, as assessed by pre-pulse inhibition (PPI) of the acoustic startle reflex. In P2X4 knockout mice, the effects of IVM in the open field and elevated plus maze were similar to those observed in wild type mice; conversely, the drug significantly increased startle amplitude and failed to reduce PPI. Taken together, these results suggest that P2X4 receptors may play a role in the regulation of sensorimotor gating.


2021 ◽  
Vol 15 ◽  
Author(s):  
Haiyan Zeng ◽  
Zijia Yu ◽  
Qingjun Huang ◽  
Haiyun Xu

Attachment insecurity in the forms of attachment anxiety and avoidance is associated with mental disorders in humans. In this research field, rodents, especially mice and rats, are commonly used to study social behaviors and underlying biological mechanisms due to their pronounced sociability. However, quantitative assessment of attachment security/insecurity in rodents has been a major challenge. The present study identified attachment insecurity behaviors in rats subjected to maternal separation (MS) during postnatal days (PD) 2–16 and early weaning (EW) during PD 17–21. This MSEW procedure has been used to mimic early life neglect in humans. After MSEW, rats continued to survive until early adulthood when they were subjected to open-field, social interaction, and elevated-plus maze tests. Compared to CNT rats in either gender, MSEW rats moved longer distances at higher velocities in the open-field. The MSEW rats also showed lower ratios of travel distance at central zone over that on whole arena of the open-field compared to CNT rats. In social interaction test, male CNT rats preferred to investigate an empty cage than females; whereas female CNT rats spent more time with a partner-containing cage as compared to males. This gender-specific difference was reversed in MSEW rats. On elevated-plus maze female CNT rats exhibited more risk-taking behaviors as compared to male counterparts. Moreover, female MSEW rats experienced a greater difficulty in making a decision on whether approaching to or averting from which arms of elevated-plus maze. Taken together, male MSEW rats behaved like attachment anxiety while females’ phenotype is alike to attachment avoidance described in humans. These results shall prompt further application of MSEW rat in abnormal psychology and biological psychiatry research.


2019 ◽  
Vol 12 (04) ◽  
pp. 2157-2165
Author(s):  
Naveen Sharma ◽  
Ajay Sharma ◽  
Vipin Kumar Sharma

This study was carried out to assess the possible effect of Passiflora edulis Sims on reserpine-induced fibromyalgia with using different animal models and commonly used in the Virginia, southern Illinois, southeast Kansas and India as a folk medicine. Possible effect of extract of the plant was evaluated on reserpine-induced fibromyalgia. For evaluating the effect of this Plant leaves extract, different models were used such as tail flick, radiant heat, hot plate and inclined plane model. Evaluation of anti-depression activity, forced swim test and elevated plus maze (EPM) model were used. Investigations were shown that reserpine-treated animals responded with significantly increased sensitivity of pain in tail flick latency, decreased threshold of paw-withdrawal and immobility time and in Randall test. Whereas Plant leaves extract at different level of doses (e.g. 200 and 400 mg/kg) has shown a significant reduction in time of immobility, withdrawal latency of tail and the significant increase in mechanical and thermal hyperalgesia. The Passiflora edulis Sims showed inhibition of algesic condition in all the models which was dose dependent. During forced swim test extract of plant showed the significant reduce immobility time as compared with the control group, also in the plus‐maze method, Plant leaves extract showed increased time spend in open arm. The results were confirmed that the use of the extract of leaves of Passiflora edulis Sims in the traditional management of pain and enhances behavioural activity.


Author(s):  
Vasudha Bakshi ◽  
Devender Palsa ◽  
Nazia Begum ◽  
Jeevan Kommidi ◽  
Kapishwar Singh ◽  
...  

Objective: The aim of this study is to investigate the effects of pterostilbene on the behavior of mice and oxidative stress under the influence of Ketamine induced schizophrenia model. Methods: Schizophrenia was induced in mice by ketamine (50mg/kg/day, i.p, for 14 days). The treatment effect of pterostilbene (10 and 20 mg/kg/day, p.o, for 14 days) were verified on Actophotometer, Y-maze, Forced swim test (FST), open field apparatus, acetylcholinesterase activity and anti oxidant stress-related biomarker (Catalase, GSH, TBARS, SOD) levels in brain tissues. Results: Pterostilbene decreased TBARS, AChE and increased SOD, CAT, GSH levels in mice brain when compared with control group. It also improved spatial recognition memory, decreased mobility time, decreased exploratory behaviour and locomotor activity as evident by improved performance in Y-Maze task, Forced swim test, Open field test and Locomotor activity test. Conclusion: Pterostilbene has a neuroprotective role related atleast in part to an antioxidant mechanism and Anti AChE activity, which could be explored as more effective therapies of schizophrenia and other psychiatric diseases.


2011 ◽  
Vol 26 (S2) ◽  
pp. 1576-1576
Author(s):  
B. Bernal-Morales ◽  
C.M. Contreras ◽  
J. Cueto-Escobedo ◽  
G. Guillén-Ruiz

IntroductionDuring gestation and maternal behavior, some physiological events can protect the dam and offspring, but explanations for such phenomena are partially unknown. The effects of stress during prenatal development and infancy can be studied in controlled laboratory conditions.ObjectiveTo determine the pre- and postnatal effects of stress on coping strategies in weanling rats subjected to the open field and forced swim tests after their dams are subjected to stress during gestation.MethodRats aged 21 postnatal days (PND) were assigned to either a Control group (n = 36; offspring from intact dams during gestation) or a Prenatal stress group (n = 36; offspring from dams forced to swim during 5 min sessions on gestational days 1, 7, 14, and 19). Both groups were tested in the open field to evaluate locomotor activity and rearing. In another experiment, PND21 intact rats assigned to a Control group (n = 26) or Postnatal stress group (n = 35) were subjected to restraint stress for 6 min prior to the tests and were later evaluated in the forced swim test.ResultsLocomotor activity (p < 0.026) and rearing (p < 0.001) were lower in the Prenatal stress group compared with the Control group. The latency to first immobility was shorter (p < 0.008), and the total immobility time was longer (p < 0.005) in the Postnatal stress group than Control group.ConclusionStress exposure during gestation produces detectable changes during weanling, consisting of reduced exploratory activity and susceptibility to despair.


Reproduction ◽  
2007 ◽  
Vol 133 (3) ◽  
pp. 663-674 ◽  
Author(s):  
Cheryl A Frye ◽  
Jason J Paris ◽  
Madeline E Rhodes

Sequential actions of 17β-estradiol (E2) and progesterone (P4) in the hypothalamus and the P4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), in the midbrain ventral tegmental area (VTA) respectively mediate the initiation and intensity of lordosis of female rats and mayalso modulate anxietyand social behaviors, through actions in these, and/or other brain regions. Biosynthesis of E2, P4, and 3α,5α-THP can also occur in brain, independent of peripheral gland secretion, in response to environmental/behavioral stimuli. The extent to which engaging in tasks related to reproductive behaviors and/or mating increased E2 or progestin concentrations in brain was investigated. In Experiment 1, proestrous rats were randomly assigned to be tested in individual tasks, including the open field, elevated plus maze, partner preference, social interaction, or no test control, in conjunction with paced mating or no mating. Engaging in paced mating, but not other behaviors, significantly increased dihydroprogesterone (DHP) and 3α,5α-THP levels in midbrain, hippocampus, striatum, and cortex. In Experiment 2, proestrous rats were tested in the combinations of the above tasks (open field and elevated plus maze, partner preference, and social interaction) with or without paced mating. As in Experiment 1, only engaging in paced mating increased DHPand 3α,5α-THP concentrations in midbrain, hippocampus, striatum, and cortex. Thus, paced mating enhances concentrations of 5α-reduced progestins in brain areas associated with reproduction (midbrain), as well as exploration/anxiety (hippocampus and striatum) and social behavior (cortex).


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