scholarly journals Oral aniracetam treatment in C57BL/6J mice without pre-existing cognitive dysfunction reveals no changes in learning, memory, anxiety or stereotypy

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1452
Author(s):  
Conner D. Reynolds ◽  
Taylor S. Jefferson ◽  
Meagan Volquardsen ◽  
Ashvini Pandian ◽  
Gregory D. Smith ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Healthy Subjects ◽  
Elevated Plus Maze ◽  
Therapeutic Benefit ◽  
Novel Object Recognition ◽  
Behavioral Testing ◽  
Novel Object ◽  
Plus Maze ◽  
Marble Burying ◽  
Enhanced Learning

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.

scholarly journals Oral aniracetam treatment in C57BL/6J mice without pre-existing cognitive dysfunction reveals no changes in learning, memory, anxiety or stereotypy

F1000Research ◽  
2018 ◽  
Vol 6 ◽  
pp. 1452 ◽  
Author(s):  
Conner D. Reynolds ◽  
Taylor S. Jefferson ◽  
Meagan Volquardsen ◽  
Ashvini Pandian ◽  
Gregory D. Smith ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Healthy Subjects ◽  
Elevated Plus Maze ◽  
Therapeutic Benefit ◽  
Novel Object Recognition ◽  
Behavioral Testing ◽  
Novel Object ◽  
Plus Maze ◽  
Marble Burying ◽  
Enhanced Learning

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.

scholarly journals Study of oral aniracetam in C57BL/6J mice without pre-existing cognitive impairments

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1452
Author(s):  
Conner D. Reynolds ◽  
Taylor S. Jefferson ◽  
Meagan Volquardsen ◽  
Ashvini Pandian ◽  
Gregory D. Smith ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Healthy Subjects ◽  
Elevated Plus Maze ◽  
Cognitive Impairments ◽  
Therapeutic Benefit ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Plus Maze ◽  
Marble Burying ◽  
Enhanced Learning

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.

scholarly journals Early-life status epilepticus induces long-term deficits in anxiety and spatial learning in mice

2017 ◽  
Vol 04 (01) ◽  
pp. 036-045
Author(s):  
Gregory Smith ◽  
Nowrin Ahmed ◽  
Erin Arbuckle ◽  
Joaquin Lugo
Keyword(s):  
Status Epilepticus ◽  
Object Recognition ◽  
Early Life ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Plus Maze ◽  
Marble Burying

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.

scholarly journals In a Preclinical Model of Prenatal Alcohol Exposure, an Iron Supplementation Intervention Reduces Anxiety-Like Behavior in Both Sexes and Improves Growth in Males

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 537-537
Author(s):  
Kaylee Helfrich ◽  
Rachel Hodges ◽  
Joshua Baulch ◽  
Sandra Mooney ◽  
Susan Smith
Keyword(s):  
Iron Deficiency ◽  
Iron Supplementation ◽  
Elevated Plus Maze ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Novel Object Recognition ◽  
The Novel ◽  
Novel Object ◽  
Plus Maze ◽  
Prenatal Alcohol

Abstract Objectives Both prenatal iron deficiency and prenatal alcohol exposure (PAE) decrease body weight, increase susceptibility to anxiety, and impair memory and learning in the offspring. PAE itself causes fetal iron deficiency, even when mothers consume sufficient iron. We hypothesized that iron supplementation in PAE pregnancies would not alter offspring growth but would improve measures of anxiety, learning, and memory. Methods Pregnant Long-Evans rats received 5 g/kg/day ethanol or isocaloric maltodextrin (split-dose) from gestational day (GD) 13.5–19.5 and received 6 mg/kg/day iron as ferric sulfate or water from GD12.5–19.5. Male and female offspring were weighed regularly after birth and underwent elevated plus maze (postnatal day (P) 27), open field (P28), novel object recognition (P29–30), T-maze (P32–40), and fear conditioning (P42–50) tests. Mixed model analysis was used to determine significance of the effects of PAE, iron, and sex. Results PAE reduced postnatal body growth in both male (P = 0.028) and female (P = 0.026) offspring. In both sexes, PAE interacted with age to affect growth (P &lt; 0.001) from P5 to P50. In males but not females, iron supplementation interacted with age (P = 0.044) and age and PAE (P = 0.045) to improve growth in PAE + iron males, such that their weights approached control weights by P50. On the elevated plus maze, iron supplementation, regardless of PAE or sex, increased time spent on the open arms by 39–118%, indicating reduced anxiety-like behavior (P = 0.030). On the open field test, time spent in the center was not affected by PAE, iron, or sex (P’s &gt; 0.200). On the novel object recognition test, at delays of both 1 and 24 hours, all groups (except MD + Iron Males with 24-hour delay) recognized the novel object better than chance (P’s &lt; 0.040), but recognition at both time delays was not affected by PAE, iron, or sex (P’s &gt; 0.120), showing that these did not affect recognition memory. On the T-maze and fear conditioning tests, which assess learning and memory, PAE, iron, and sex had no effect on the results (P’s &gt; 0.080). Conclusions This work is the first to investigate gestational iron supplementation as an intervention for alcohol-exposed pregnancies. These results suggest iron supplementation may improve outcomes such as growth in males and anxiety in both sexes in alcohol-exposed populations. Funding Sources NIAAA NIDDK.

scholarly journals Modification of NO-cGMP Pathway Differentially Affects Diazepam- and Flunitrazepam-Induced Spatial and Recognition Memory Impairments in Rodents

2019 ◽  
Vol 37 (4) ◽  
pp. 1036-1046 ◽  
Author(s):  
Jolanta Orzelska-Górka ◽  
Piotr Bernat ◽  
Piotr Tutka ◽  
Joanna Listos ◽  
Ewa Kędzierska ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Recognition Memory ◽  
Animal Behavior ◽  
Memory Impairment ◽  
Elevated Plus Maze ◽  
Novel Object Recognition ◽  
Novel Object ◽  
Memory Impairments ◽  
Plus Maze ◽  
Cgmp Pathway

AbstractThis study investigated the influence of sildenafil and methylene blue (MB), two modulators of the nitric oxide (NO)-cyclic guanosine-3′,5′-monophosphate (cGMP) pathway on amnesic effects of two benzodiazepines (BZs) (diazepam (DZ) and flunitrazepam (FNZ)), in rodents—mice and rats. In the modified elevated plus maze (mEPM) and novel object recognition (NOR) tests, MB given ip at a dose of 5 mg/kg 5 min prior to DZ administration (0.25 or 1 mg/kg, sc) enhanced/induced memory impairment caused by DZ. When MB (2.5, 5, and 10 mg/kg) was applied 5 min prior to FNZ administration (0.05 and 0.1 mg/kg), an effect was opposite and memory impairment induced by FNZ was reduced. When sildenafil (2.5 and 5 mg/kg, ip) was applied 5 min prior to DZ, we observed a reduction of DZ-induced memory deficiency in the mEPM test. A similar effect of sildenafil was shown in the NOR test when the drug was applied at doses of 1.25, 2.5, and 5 mg/kg prior to DZ. In the mEPM test, sildenafil at abovementioned doses had no effects on FNZ-induced memory impairment. In turns, sildenafil administered at doses of 2.5 and 5 mg/kg increased the effect of FNZ on memory impairment in the NOR test. In conclusion, the NO-cGMP pathway is involved differentially into BZs-induced spatial and recognition memory impairments assessed using the NOR and mEPM tests. Modulators of the NO-cGMP pathway affect animal behavior in these tests in a different way depending on what benzodiazepine is applied.

Neuropharmacological Characterization of Dioclea altissima Seed Lectin (DAL) in Mice: Evidence of Anxiolytic-like Effect Mediated by Serotonergic, GABAergic Receptors and NO Pathway

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 ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Elevated Plus Maze ◽  
Biological Activities ◽  
Plant Lectins ◽  
Plus Maze ◽  
Marble Burying ◽  
Gabaergic Receptors ◽  
The Central Nervous System ◽  
Hole Board

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.

scholarly journals Involvement of 5-HT1AReceptors in the Anxiolytic-Like Effects of Quercitrin and Evidence of the Involvement of the Monoaminergic System

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jian Li ◽  
Qian-tong Liu ◽  
Yi Chen ◽  
Jie Liu ◽  
Jin-li Shi ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Elevated Plus Maze ◽  
Experimental Models ◽  
Control Group ◽  
Repeated Treatment ◽  
Plus Maze ◽  
Way 100635 ◽  
Marble Burying ◽  
Monoaminergic System ◽  
Light Dark Box

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.

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 ◽  
...  
Keyword(s):  
Risk Taking ◽  
Social Behaviour ◽  
Elevated Plus Maze ◽  
Imprinted Genes ◽  
Wild Type ◽  
Wild Type Littermate ◽  
Plus Maze ◽  
Marble Burying ◽  
Compulsive Behaviour

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.

Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice

2015 ◽  
Vol 28 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Hila M Ene ◽  
Nirit Z Kara ◽  
Noa Barak ◽  
Tal Reshef Ben-Mordechai ◽  
Haim Einat
Keyword(s):  
Open Field ◽  
Atypical Antipsychotic ◽  
Antipsychotic Drugs ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Serotonergic Receptors ◽  
Serotonin System ◽  
Plus Maze ◽  
Marble Burying ◽  
Behavioural Tests

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.

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