scholarly journals Interaction between perineuronal nets and ketamine in antidepressant action

2021 ◽  
Author(s):  
Calvin K Young ◽  
Kachina G Kinley ◽  
Neil McNaughton
Keyword(s):  
Suicide Risk ◽  
Forced Swim Test ◽  
Perineuronal Nets ◽  
Scaffolding Proteins ◽  
Infralimbic Cortex ◽  
Swim Test ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Antidepressant Action

Depression is highly prevalent, increases suicide risk, and is now the leading cause of disability worldwide. Our ability to treat depression is hampered by the lack of understanding of its biological underpinnings and of the mode of action of effective treatments. We hypothesised that the scaffolding proteins in the medial frontal cortex play a major role in effective antidepressant action. We implanted cannulae into the infralimbic cortex to inject chABC and locally remove perineuronal nets and then tested for antidepressant effects with the forced swim test. We further tested if systemic injections of ketamine had an additive effect. Our preliminary data indicate that neither the removal of these scaffolding proteins nor ketamine were sufficient to decrease depression-like behaviour, but may interact synergistically to decrease immobility time in the forced swim test.

scholarly journals Antidepressant effects of an inverse agonist selective for α5 GABA-A receptors in the rat forced swim test

2014 ◽  
Vol 64 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Janko Samardžić ◽  
Laslo Puškaš ◽  
Miljana Obradović ◽  
Dijana Lazić-Puškaš
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Digital Camera ◽  
Repeated Administration ◽  
Inverse Agonist ◽  
Gaba A ◽  
Swim Test ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time

Abstract It has been shown in electrophysiological studies that the ligand L-655,708 possesses a binding selectivity and a moderate inverse agonist functional selectivity for α5-containing GABA-A receptors. The present study is aimed to investigate the antidepressant effects of the ligand L-655,708 in the forced swim test (FST) and its impact on locomotor activity in rats. The behavior of the animals was recorded with a digital camera, and the data were analyzed by one-way ANOVA, followed by Dunnett’s test. In FST, L-655,708 significantly decreased immobility time at a dose of 3 mg/kg after a single and repeated administration (p<0.05), exerting acute and chronic antidepressant effects. However, it did not induce significant differences in the time of struggling behavior during FST. Furthermore, L-655,708 did not show a significant effect on locomotor activity (p>0.05). These data suggest that negative modulation at GABA-A receptors containing the α5 subunit may produce antidepressant effects in rats. These effects were not confounded by locomotor influences.

scholarly journals Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine

2018 ◽  
Vol 33 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Jaclyn N Highland ◽  
Patrick J Morris ◽  
Panos Zanos ◽  
Jacqueline Lovett ◽  
Soumita Ghosh ◽  
...  
Keyword(s):  
Oral Administration ◽  
Learned Helplessness ◽  
Oral Bioavailability ◽  
Forced Swim Test ◽  
Abuse Potential ◽  
Absolute Bioavailability ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Antidepressant Efficacy

Background: ( R,S)-ketamine has gained attention for its rapid-acting antidepressant actions in patients with treatment-resistant depression. However, widespread use of ketamine is limited by its side effects, abuse potential, and poor oral bioavailability. The ketamine metabolite, ( 2R,6R)-hydroxynorketamine, exerts rapid antidepressant effects, without ketamine’s adverse effects and abuse potential, in rodents. Methods: We evaluated the oral bioavailability of ( 2R,6R)-hydroxynorketamine in three species (mice, rats, and dogs) and also evaluated five candidate prodrug modifications for their capacity to enhance the oral bioavailability of ( 2R,6R)-hydroxynorketamine in mice. Oral administration of ( 2R,6R)-hydroxynorketamine was assessed for adverse behavioral effects and for antidepressant efficacy in the mouse forced-swim and learned helplessness tests. Results: ( 2R,6R)-hydroxynorketamine had absolute bioavailability between 46–52% in mice, 42% in rats, and 58% in dogs. Compared to intraperitoneal injection in mice, the relative oral bioavailability of ( 2R,6R)-hydroxynorketamine was 62%, which was not improved by any of the candidate prodrugs tested. Following oral administration, ( 2R,6R)-hydroxynorketamine readily penetrated the brain, with brain to plasma ratios between 0.67–1.2 in mice and rats. Oral administration of ( 2R,6R)-hydroxynorketamine to mice did not alter locomotor activity or precipitate behaviors associated with discomfort, sickness, or stereotypy up to a dose of 450 mg/kg. Oral ( 2R,6R)-hydroxynorketamine reduced forced-swim test immobility time (15–150 mg/kg) and reversed learned helplessness (50–150 mg/kg) in mice. Conclusions: These results demonstrate that ( 2R,6R)-hydroxynorketamine has favorable oral bioavailability in three species and exhibits antidepressant efficacy following oral administration in mice.

Failure to detect the action of antidepressants in the forced swim test in Swiss mice

2017 ◽  
Vol 30 (3) ◽  
pp. 158-167 ◽  
Author(s):  
Patrick R. Suman ◽  
Nathalia Zerbinatti ◽  
Lais Cristina Theindl ◽  
Karolina Domingues ◽  
Cilene Lino de Oliveira
Keyword(s):  
Sodium Butyrate ◽  
Antidepressant Treatment ◽  
Forced Swim Test ◽  
Dark Cycle ◽  
Swim Test ◽  
Swiss Mice ◽  
Forced Swim ◽  
Immobility Time ◽  
Effective Doses ◽  
High Doses

ObjectiveThe aims of this study were to replicate previously published experiments and to modify the protocol to detect the effects of chronic antidepressant treatment in mice.MethodsMale Swiss mice (n=6–8/group) housed in reversed light/dark cycle were randomly assigned into receive vehicle (10% sucrose), sub-effective doses (1 and 3 mg/kg) or effective doses (10 and 30 mg/kg) of bupropion, desipramine, and fluoxetine and a candidate antidepressant, sodium butyrate (1–30 mg/kg) per gavage (p.o.) 1 h before the forced swim test (FST). Treatments continued daily for 7 and 14 days during retests 1 and 2, respectively. In an additional experiment, mice received fluoxetine (20 mg/kg) or vehicle (10% sucrose or 0.9% saline) p.o. or i.p. before the FST. Mice housed in reversed or standard light/dark cycles received fluoxetine (20 mg/kg) prior FST. Video recordings of behavioural testing were used for blind assessment of the outcomes.ResultsAccording to the expected, doses of antidepressants considered sub-effective failed to affect the immobility time of mice in the FST. Surprisingly, acute and chronic treatment with the high doses of bupropion, desipramine, and fluoxetine or sodium butyrate also failed to reduce the immobility time of mice in the FST. Fluoxetine 20 mg/kg was also ineffective in the FST when injected i.p. or in mice housed in normal light/dark cycle.ConclusionData suggest the lack of efficacy of orally administered bupropion, desipramine, fluoxetine in the FST in Swiss mice. High variability, due to high and low immobility mice, may explain the limited effects of the treatments.

scholarly journals Evaluation of Additive or Synergistic Effect of Piper nigram and Ocimum sanctum Extracts for their Antidepressant Activity

2021 ◽  
Vol 70 (2) ◽  
Author(s):  
K. Mohana Rao ◽  
Siva B. ◽  
Mahendra U. ◽  
Vinay K. ◽  
A. Narendra Babu ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Antidepressant Activity ◽  
Piper Nigrum ◽  
Ocimum Sanctum ◽  
Alcoholic Extract ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time ◽  
Wide Range

Depression is a state of excessive sensitivity to criticism, fear of rejections, lack of self-interest, loss of pleasure. In the traditional systems of medicine, many plants and formulations have been used to treat depression for thousands of years. In recent times, research on the plants increased globally and so many plants provide the evidence to cure diseases. Ocimum sanctum, popularly known as Tulsi is one of the sacred herbs for Hindus in the Indian subcontinent. It has a versatile role in traditional medicine. The fruits of Piper nigrum are used to make black pepper. This hotly pungent spice is one of the earliest known and most widely used spices in the world today. Wide range of animal tests for antidepressant agents are commonly used. The Forced swim test and Tail suspension test in mice were mostly used. Hence in the present study Forced swim test was used as animal model of depression. In present study immobility time in Forced swim test was significantly decreased by a combination of Piper nigrum fruit extract and Ocimum sanctum extract treated groups compared to control group. The combination of extracts (50 mg/kg each) activity was comparable to standard drug Fluoxetine. Treatment with extracts does not modify the locomotor activity of mice, which indicates that they exert antidepressant effects without modifying significantly locomotor activity. Therefore, the present study confirms the combination of alcoholic extract of Piper nigrum (AEPN) fruit and aqueous extract of Ocimum sanctum (AEOS) possessing additive/synergistic antidepressant activity.

scholarly journals Evaluation of antidepressant activity of tramadol in comparison with imipramine in Swiss albino mice

2017 ◽  
Vol 6 (3) ◽  
pp. 695
Author(s):  
Chiranjeevi Bonda ◽  
Sudhir Pawar ◽  
Jaisen Lokhande
Keyword(s):  
Forced Swim Test ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Tail Suspension ◽  
Swim Test ◽  
Forced Swim ◽  
Group I ◽  
Immobility Time ◽  
Suspension Test

Background: The aim of the study was to evaluate the antidepressant effect of opioid analgesic tramadol using forced swim test and tail suspension test models.Methods: The antidepressant effect was assessed by recording the immobility time in Forced swim test (FST) and Tail suspension test (TST). The mice were randomly divided into five groups. Mice belonging to group I was given normal saline (0.1ml/kg) which acted as control. Group II received imipramine (15mg/kg) considered as the standard drug tramadol was given in graded dose (10, 20 and 40 mg/kg) to mice of groups III, IV, V respectively. All drugs were administered intraperitoneally for seven successive days; test was done on 7th day.Results: Tramadol and Imipramine showed antidepressant activity when compared to control. There is dose dependent increase in antidepressant activity of tramadol. The antidepressant activity of imipramine was significantly (P<0.05) more than tramadol at dose 10 and 20 mg/kg but antidepressant activity with tramadol 40mg/kg was comparable to imipramine treated mice.Conclusions: The results of this study indicated the presence of antidepressant activity of tramadol at 40mg/kg.

scholarly journals Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4218 ◽  
Author(s):  
Koprdova ◽  
Csatlosova ◽  
Durisova ◽  
Bogi ◽  
Majekova ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Behavioral Assessment ◽  
Dopamine Neurons ◽  
Neuroleptic Drug ◽  
Swim Test ◽  
Forced Swim ◽  
Reuptake Inhibition ◽  
Immobility Time ◽  
Dopamine Reuptake

SMe1EC2M3 is a pyridoindole derivative related to the neuroleptic drug carbidine. Based on the structural similarities of SMe1EC2M3 and known serotonin (5-HT), norepinephrine, and dopamine reuptake inhibitors, we hypothesized that this compound may also have triple reuptake inhibition efficacy and an antidepressant-like effect. PreADMET and Dragon software was used for in silico prediction of pharmacokinetics and pharmacodynamics of SMe1EC2M3. Forced swim test was used to evaluate its antidepressant-like effects. Extracellular in vivo electrophysiology was used to assess 5-HT, norepinephrine, and dopamine reuptake inhibition efficacy of SMe1EC2M3. PreADMET predicted reasonable intestinal absorption, plasma protein binding, and blood-brain permeability for SMe1EC2M3. Dragon forecasted its efficiency as an antidepressant. Using behavioral measurements, it was found that SMe1EC2M3 decreased immobility time and increase swimming time during the forced swim test (FST). Electrophysiological investigations showed that SMe1EC2M3 dose-dependently suppressed the excitability of 5-HT neurons of the dorsal raphe nucleus (DRN), norepinephrine neurons of the locus coeruleus (LC), and dopamine neurons of the ventral tegmental area (VTA). The SMe1EC2M3-induced suppression of 5-HT, norepinephrine, and dopamine neurons was reversed by the antagonists of serotonin-1A (5-HT1A; WAY100135), α-2 adrenergic (α2, yohimbine), and dopamine-2 receptors (D2, haloperidol), respectively. We conclude that SMe1EC2M3 is prospective triple 5-HT, norepinephrine, and dopamine reuptake inhibitor with antidepressant-like properties, however future studies should be performed to complete the pharmacological profiling of this compound.

Both increases in immature dentate neuron number and decreases of immobility time in the forced swim test occurred in parallel after environmental enrichment of mice

Neuroscience ◽  
2007 ◽  
Vol 147 (3) ◽  
pp. 631-638 ◽  
Author(s):  
M.V. Llorens-Martín ◽  
N. Rueda ◽  
C. Martínez-Cué ◽  
I. Torres-Alemán ◽  
J. Flórez ◽  
...  
Keyword(s):  
Environmental Enrichment ◽  
Forced Swim Test ◽  
Neuron Number ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time

scholarly journals Effect of Passiflora Edulis Sims onReserpine Induced Fibromyalgia

2019 ◽  
Vol 12 (04) ◽  
pp. 2157-2165
Author(s):  
Naveen Sharma ◽  
Ajay Sharma ◽  
Vipin Kumar Sharma
Keyword(s):  
Forced Swim Test ◽  
Control Group ◽  
Tail Flick ◽  
Plant Leaves ◽  
Passiflora Edulis ◽  
Swim Test ◽  
Forced Swim ◽  
Plus Maze ◽  
Immobility Time ◽  
Passiflora Edulis Sims

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.

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