scholarly journals Mice carrying paternal knockout of imprinted Grb10 do not show compulsive behaviours

2020 ◽  
Author(s):  
Kira DA Rienecker ◽  
Alexander T Chavasse ◽  
Kim Moorwood ◽  
Andrew Ward ◽  
Trevor Humby ◽  
...  

ABSTRACTMice lacking paternal expression of imprinted Grb10 show a number of social behaviour deficits, including an enhanced allogrooming phenotype. However, this could also index compulsive behaviour, and the increased whisker barbering seen in Grb10+/p mice has been suggested to be indicative of a trichotillomania-type behaviour. Here we test whether compulsive behaviour is a more general phenotype in Grb10+/p mice by examining marble burying at three different adult ages (2, 6 and 10 months). We also examined the mice for potentially confounding anxiety phenotypes using the elevated plus maze (EPM). Grb10+/p mice showed no difference from wild-type littermate controls on any measure in the marble burying test at any age. There was no difference in standard anxiety measures either, although Grb10+/p mice displayed more risk-taking behaviours on the EPM than wild-type mice. These data suggest that Grb10+/p mice are not generally more compulsive, and that the enhanced allogrooming is probably indicative of altered social behaviour. Furthermore, the altered behaviours seen on the EPM adds to other published findings suggesting that Grb10, and imprinted genes more generally, have a role in mediating risk-taking behaviour.

2020 ◽  
Vol 26 (31) ◽  
pp. 3895-3904
Author(s):  
João R.C. Araújo ◽  
Adriana R. Campos ◽  
Marina de Barros M.V. Damasceno ◽  
Sacha A.A.R. Santos ◽  
Maria K.A. Ferreira ◽  
...  

Background: Plant lectins have shown promising biological activities in the central nervous system (CNS). Objective: This study evaluated the effect of DAL, a lectin isolated from the seeds of the Dioclea altissima species, having binding affinity to D-glucose or D-mannose residues, on mice behavior. Methods: Mice (n=6/group) were treated (i.p.) with DAL (0.25, 0.5 or 1 mg/kg) or vehicle and subjected to several tests (open field/OFT, marble-burying/MBT, hole-board/HBT, elevated plus maze/PMT, tail suspension/ TST, forced swimming/FST or rotarod/RRT). Pizotifen, cyproheptadine, flumazenil, L-NAME, 7-NI, Larginine or yohimbine were administered 15 min before DAL (0.5 mg/kg) and the animals were evaluated on PMT. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. Results: The results showed there were no neurobehavioral changes in the mice at the RRT, FST and locomotion in the OFT. DAL (0.25, 0.5 or 1 mg/kg) increased the behavior of grooming and rearing in the OFT, head dips in the HBT, pedalling in the TST and decreased the number of marbles hidden in the MBT. In the PMT, DAL (0.25, 0.5 and 1 mg/kg) and Diazepam increased the frequency of entries in the open arms and the time of permanence in the open arms without affecting the locomotor activity. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and it prevented by pizotifen, cyproheptadine, flumazenil, L-NAME and 7-NI, but not by L-arginine or yohimbine. Conclusion: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors and NO pathway.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jian Li ◽  
Qian-tong Liu ◽  
Yi Chen ◽  
Jie Liu ◽  
Jin-li Shi ◽  
...  

Quercitrin is a well-known flavonoid that is contained in Flos Albiziae, which has been used for the treatment of anxiety. The present study investigated the anxiolytic-like effects of quercitrin in experimental models of anxiety. Compared with the control group, repeated treatment with quercitrin (5.0 and 10.0 mg/kg/day, p.o.) for seven days significantly increased the percentage of entries into and time spent on the open arms of the elevated plus maze. In the light/dark box test, quercitrin exerted an anxiolytic-like effect at 5 and 10 mg/kg. In the marble-burying test, quercitrin (5.0 and 10.0 mg/kg) also exerted an anxiolytic-like effect. Furthermore, quercitrin did not affect spontaneous locomotor activity. The anxiolytic-like effects of quercitrin in the elevated plus maze and light/dark box test were blocked by the serotonin-1A (5-hydroxytryptamine-1A (5-HT1A)) receptor antagonist WAY-100635 (3.0 mg/kg, i.p.) but not by theγ-aminobutyric acid-A (GABAA) receptor antagonist flumazenil (0.5 mg/kg, i.p.). The levels of brain monoamines (5-HT and dopamine) and their metabolites (5-hydroxy-3-indoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid) were decreased after quercitrin treatment. These data suggest that the anxiolytic-like effects of quercitrin might be mediated by 5-HT1Areceptors but not by benzodiazepine site of GABAAreceptors. The results of the neurochemical studies suggest that these effects are mediated by modulation of the levels of monoamine neurotransmitters.


2015 ◽  
Vol 28 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Hila M Ene ◽  
Nirit Z Kara ◽  
Noa Barak ◽  
Tal Reshef Ben-Mordechai ◽  
Haim Einat

ObjectiveA number of atypical antipsychotic drugs were demonstrated to have anxiolytic effects in patients and in animal models. These effects were mostly suggested to be the consequence of the drugs’ affinity to the serotonin system and its receptors. Asenapine is a relatively new atypical antipsychotic that is prescribed for schizophrenia and for bipolar mania. Asenapine has a broad pharmacological profile with significant effects on serotonergic receptors, hence it is reasonable to expect that asenapine may have some anxiolytic effects. The present study was therefore designed to examine possible effects of asenapine on anxiety-like behaviour of mice.MethodMale ICR mice were repeatedly treated with 0.1 or 0.3 mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus-maze (EPM), defensive marble burying and hyponeophagia tests. In an adjunct experiment, we tested the effects of acute diazepam in the same test battery.ResultsThe results show that diazepam reduced anxiety-like behaviour in the EPM, the defensive marble burying test and the hyponeophagia test but not in the open field. Asenapine has anxiolytic-like effects in the EPM and the defensive marble burying tests but had no effects in the open-field or the hyponeophagia tests. Asenapine had no effects on locomotor activity.ConclusionThe results suggest that asenapine may have anxiolytic-like properties and recommends that clinical trials examining such effects should be performed.


2017 ◽  
Vol 31 (10) ◽  
pp. 1334-1346 ◽  
Author(s):  
Morgane Milienne-Petiot ◽  
Lucianne Groenink ◽  
Arpi Minassian ◽  
Jared W Young

Background: Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D1-family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Methods: Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D1-family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Results: Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Conclusions: Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D1-family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D1-family receptors supports the hypothesis that D1 and/or D5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1452
Author(s):  
Conner D. Reynolds ◽  
Taylor S. Jefferson ◽  
Meagan Volquardsen ◽  
Ashvini Pandian ◽  
Gregory D. Smith ◽  
...  

Background: The piracetam analog, aniracetam, has recently received attention for its cognition enhancing potential, with minimal reported side effects.  Previous studies report the drug to be effective in both human and non-human models with pre-existing cognitive dysfunction, but few studies have evaluated its efficacy in healthy subjects. A previous study performed in our laboratory found no cognitive enhancing effects of oral aniracetam administration 1-hour prior to behavioral testing in naïve C57BL/6J mice. Methods: The current study aims to further evaluate this drug by administration of aniracetam 30 minutes prior to testing in order to optimize any cognitive enhancing effects. In this study, all naïve C57BL/6J mice were tested in tasks of delayed fear conditioning, novel object recognition, rotarod, open field, elevated plus maze, and marble burying. Results: Across all tasks, animals in the treatment group failed to show enhanced learning when compared to controls. Conclusions: These results provide further evidence suggesting that aniracetam conveys no therapeutic benefit to subjects without pre-existing cognitive dysfunction.


2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Edvaldo Rodrigues de Almeida ◽  
Krissia Rayane de Oliveira Rafael ◽  
Geraldo Bosco Lindoso Couto ◽  
Ana Beatriz Matos Ishigami

The aim of the present study is to demonstrate the anxiolytic and anticonvulsant effects of a hydroalcoholic extract obtained from the aerial parts ofCissus sicyoidesL. (CS) (Vitaceae) on male and female mice using several behavioral assays. Groups of males and females treated via intraperitoneal (IP) with doses of 300, 600, and 1000 mg/kg of the extract showed significant action in the elevated plus-maze (EPM), time spent in the open arms, and number of entries in the open arms. The board-hole test also showed a significant increase in the time spent in head-dipping and in marble-burying test of the number of marbles buried. The same treatment increased the duration of sleeping time induced by sodium pentobarbital and also showed a significant increase in protection against pentylenotetrazole-induced convulsions. These results indicate an anxiolytic and anticonvulsant-like action fromC. sicyoidesL. extract on mice, probably due to the action of flavonoid(s), Linalool, and -tocopherol present in theC. sicyoidesleaves.


2018 ◽  
Vol 129 (5) ◽  
pp. 1286-1294 ◽  
Author(s):  
Gentian Toshkezi ◽  
Michele Kyle ◽  
Sharon L. Longo ◽  
Lawrence S. Chin ◽  
Li-Ru Zhao

OBJECTIVETraumatic brain injury (TBI) is a major cause of long-term disability and death in young adults. The lack of pharmaceutical therapy for post–acute TBI recovery remains a crucial medical challenge. Stem cell factor (SCF) and granulocyte colony–stimulating factor (G-CSF), which are 2 key hematopoietic growth factors, have shown neuroprotective and neurorestorative effects in experimental stroke. The objective of this study was to determine the therapeutic efficacy of combined treatment (SCF + G-CSF) in subacute TBI.METHODSYoung-adult male C57BL mice were subject to TBI in the cortex of the right hemisphere. After TBI induction, mice were randomly divided into 2 groups: a vehicle control group and an SCF + G-CSF treatment group. Mice without TBI served as sham operative controls. Treatment was initiated 2 weeks after TBI induction. SCF (200 μg/kg) and G-CSF (50 μg/kg) or an equal volume of vehicle solution was subcutaneously injected daily for 7 days. A battery of neurobehavioral tests for evaluation of memory and cognitive function (water maze and novel object recognition tests), anxiety (elevated plus maze test), and motor function (Rota-Rod test) was performed during the period of 2–9 weeks after treatment. Neurodegeneration and dendritic density in both hemispheres were determined through histochemistry and immunohistochemistry at 11 weeks posttreatment.RESULTSWater maze testing showed that TBI-impaired spatial learning and memory was restored by SCF + G-CSF treatment. The findings from the elevated plus maze tests revealed that SCF + G-CSF treatment recovered TBI-caused anxiety and risk-taking behavior. There were no significant differences between the treated and nontreated TBI mice in both the Rota-Rod test and novel object recognition test. In the brain sections, the authors observed that widespread degenerating neurons were significantly increased in both hemispheres in the TBI-vehicle control mice. TBI-induced increases in neurodegeneration were significantly reduced by SCF + G-CSF treatment in the contralateral hemisphere, making it no different from that of the sham controls. Dendritic density in the frontal cortex of the contralateral hemisphere was significantly reduced in the TBI-vehicle control mice, whereas SCF + G-CSF–treated TBI mice showed significant increases of the dendritic density in the same brain region. SCF + G-CSF–treated TBI mice also showed a trend toward increasing dendritic density in the contralateral hippocampus.CONCLUSIONSSCF + G-CSF treatment in the subacute phase of TBI restored TBI-impaired spatial learning and memory, prevented posttraumatic anxiety and risk-taking behavior, inhibited TBI-induced neurodegeneration, and enhanced neural network remodeling. These findings suggest the therapeutic potential of hematopoietic growth factors for brain repair in the subacute phase of TBI.


2017 ◽  
Vol 04 (01) ◽  
pp. 036-045
Author(s):  
Gregory Smith ◽  
Nowrin Ahmed ◽  
Erin Arbuckle ◽  
Joaquin Lugo

Abstract Background One of the most devastating aspects of developmental epilepsy is the long-term impact on behavior. Children with epilepsy show a high co-morbidity with anxiety disorders and autism. Methods To examine whether early-life status epilepticus results in altered anxiety, repetitive behavior, social behavior, and learning and memory, we induced status epilepticus in male C57BL/6 mice on postnatal day (PD) 10. The mice received intraperitoneal injections of either kainic acid (2 mg/kg) or 0.9% normal saline. We also included a nontreated control group. Kainic acid induced status epilepticus for approximately 1.5 h. At PD60, the adult mice were then tested in a battery of behavioral tasks, including open field activity, elevated-plus maze, light-dark test, marble burying, social chamber, social partition, conditioned fear, novel object recognition, and Morris water maze. Results The early-life seizure group showed consistent increases in anxiety in the open field test (p < 0.05), elevated plus maze (p < 0.05), and light-dark task (p < 0.01). The seizure group showed significant (p < 0.01) impairment in the Morris water maze. There were no differences observed in marble burying, social partition, social chamber, novel object recognition, or delay fear conditioning tasks. Conclusions These results demonstrate that a single insult of status epilepticus during the neonatal period is sufficient to cause specific, long-term impairments in anxiety and spatial learning.


2021 ◽  
Vol 10 (4) ◽  
pp. 3479-3483
Author(s):  
Rupali A Patil

Behavioral models such as the elevated plus maze (EPM), light and dark method, Hole-board method, and Marble burying method were used to assess Methanolic extract of Mucuna pruriens seeds (MEMP) for anxiolytic function. MEMP in a dose of 200 and 300 mg/kg, p.o. was found to possess significant anxiolytic activity. In TST and FST, MEMP showed a substantial reduction in the time of immobility, indicating antidepressant action. MEMP significantly increased the latency for straub tail, extensor, myoclonic jerk, clonic convulsion and stupor in pentylenetetrazol (PTZ) and isoniazid-induced convulsion models. MEMP may be interfering with the level of monoamines; L-dopa, serotonin and histamine and produced antidepressant activity.


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