scholarly journals A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats

2011 ◽  
Vol 115 (4) ◽  
pp. 812-821 ◽  
Author(s):  
Jing Wang ◽  
Yossef Goffer ◽  
Duo Xu ◽  
David S. Tukey ◽  
D. B. Shamir ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Forced Swim Test ◽  
Preference Test ◽  
Sucrose Preference ◽  
Spared Nerve Injury ◽  
Chronic Neuropathic Pain ◽  
Swim Test ◽  
Forced Swim ◽  
Sucrose Preference Test

Background Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its antinociceptive properties. Methods The authors examined whether the spared nerve injury model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats spared nerve injury-induced depression. Results Spared nerve injury-treated rats, compared with control rats, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10 mg/kg) did not alter spared nerve injury-induced hypersensitivity; however, it treated spared nerve injury-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control rats 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control rats 5 days after administration). Conclusions Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain.

scholarly journals THE EFFECT OF PROTEASE-ACTIVATED RECEPTORS 1 INHIBITION ON DEPRESSIVE-LIKE BEHAVIOR IN THE LATENT STAGE OF FORMATION OF TEMPORAL LOBE EPILEPSY

2020 ◽  
Vol 66 (5) ◽  
pp. 17-22
Author(s):  
М. Semenikhina ◽  
◽  
M. Fedoryuk ◽  
R. Bogovik ◽  
◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Forced Swim Test ◽  
Preference Test ◽  
Control Group ◽  
Protease Activated Receptors ◽  
Swim Test ◽  
Latent Stage ◽  
Forced Swim ◽  
Pilocarpine Model

Here we investigate the effect of pharmacological blockade of protease-activated receptors 1 (PAR1) on depressive-like behavioral impairments following status epilepticus (SE). Behavioral tests were performed during the latent stage of formation of temporal lobe epilepsy two weeks after SE induced using lithium-pilocarpine model. The PAR1 blocker (SCH 79797) was injected for 10 days after SE. The results indicate a partial normalization of depressive-like behavior in the forced swim test: the climbing time was 180 s after PAR1 inhibition, and 87 s after SE). We also observed behavioral normalization after PAR1 inhibition in the sucrose test. PAR1 inhibition led to the normalization of climbing time in the forced swim test, as well as normalized the behavior in the sucrose preference test. At the same time, the swimming time in the forced swim test decreased due to the PAR1 inhibition compared to the control group, while the floating time increased.

scholarly journals Diminished responses to monoaminergic antidepressants but not ketamine in a mouse model for neuropsychiatric lupus

2018 ◽  
Vol 33 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Bettadapura N Srikumar ◽  
Pattipati S Naidu ◽  
Narasimharaju Kalidindi ◽  
Mahesh Paschapur ◽  
Bharath Adepu ◽  
...  
Keyword(s):  
Wheel Running ◽  
Forced Swim Test ◽  
Sucrose Preference ◽  
Acute Administration ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time ◽  
Resistant Depression

Background: A significant proportion of patients suffering from major depression fail to remit following treatment and develop treatment-resistant depression. Developing novel treatments requires animal models with good predictive validity. MRL/lpr mice, an established model of systemic lupus erythematosus, show depression–like behavior. Aims: We evaluated responses to classical antidepressants, and associated immunological and biochemical changes in MRL/lpr mice. Methods and results: MRL/lpr mice showed increased immobility in the forced swim test, decreased wheel running and sucrose preference when compared with the controls, MRL/MpJ mice. In MRL/lpr mice, acute fluoxetine (30 mg/kg, intraperitoneally (i.p.)), imipramine (10 mg/kg, i.p.) or duloxetine (10 mg/kg, i.p.) did not decrease the immobility time in the Forced Swim Test. Interestingly, acute administration of combinations of olanzapine (0.03 mg/kg, subcutaneously)+fluoxetine (30 mg/kg, i.p.) or bupropion (10 mg/kg, i.p.)+fluoxetine (30 mg/kg, i.p.) retained efficacy. A single dose of ketamine but not three weeks of imipramine (10 mg/kg, i.p.) or escitalopram (5 mg/kg, i.p.) treatment in MRL/lpr mice restored sucrose preference. Further, we evaluated inflammatory, immune-mediated and neuronal mechanisms. In MRL/lpr mice, there was an increase in autoantibodies’ titers, [3H]PK11195 binding and immune complex deposition. There was a significant infiltration of the brain by macrophages, neutrophils and T-lymphocytes. p11 mRNA expression was decreased in the prefrontal cortex. Further, there was an increase in the 5-HT2aR expression, plasma corticosterone and indoleamine 2,3-dioxygenase activity. Conclusion: In summary, the MRL/lpr mice could be a useful model for Treatment Resistant Depression associated with immune dysfunction with potential to expedite antidepressant drug discovery.

scholarly journals Contralateral Electroacupuncture Relieves Chronic Neuropathic Pain in Rats with Spared Nerve Injury

2018 ◽  
Vol 24 ◽  
pp. 2970-2974 ◽  
Author(s):  
Haolin Zhang ◽  
Jungang Sun ◽  
Xiyan Xin ◽  
Zejun Huo ◽  
Dong Li
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Spared Nerve Injury ◽  
Chronic Neuropathic Pain

Depression Assessment in Clinical Trials and Pre-clinical Tests: A Critical Review

2018 ◽  
Vol 18 (19) ◽  
pp. 1677-1703 ◽  
Author(s):  
Miguel F. Ferreira ◽  
Lígia Castanheira ◽  
Ana M. Sebastião ◽  
Diogo Telles-Correia
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Forced Swim Test ◽  
Antidepressant Drug ◽  
Preference Test ◽  
New Drugs ◽  
Structured Interviews ◽  
Swim Test ◽  
Forced Swim ◽  
Specific Protocol

Depression is deeply rooted in human behavior. The development of new antidepressants demands the creation of animal models to investigate new drugs, which potentially could work as antidepressants. The aim of this review is to discuss the different ways of assessing depression in clinical research, including clinical trials, and the different animal behavioral tests used to study depression and test the efficacy of antidepressants in pre-clinical studies. In clinical practice, a categorical classification, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Statistical Classification of Diseases and Related Health Problems (ICD) can be used for diagnosis, through the use of structured and semi-structured interviews. On the other hand, depression can also be assessed using a dimensional approach, through self- or clinicianrated questionnaires. Regarding the assessment of the efficacy of antidepressants in animal models, several tests are routinely used, namely the Forced Swim Test, the Modified Forced Swim Test, the Tail Suspension Test and the Sucrose Preference Test. These tests are informative, providing that the following rules are taken into account: 1) more than one test is used, with coherent results; 2) secondary drug effects, the most frequent being putative changes in motor activity, are taken into account and properly controlled with specific tests run concomitantly; 3) each test and specific protocol is validated with data from at least a gold standard antidepressant drug. We herein briefly discuss the potential and limitations of each of those tests.

scholarly journals The influence of rat strain on the development of neuropathic pain and comorbid anxio-depressive behaviour after nerve injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sara Hestehave ◽  
Klas S. P. Abelson ◽  
Tina Brønnum Pedersen ◽  
David P. Finn ◽  
Daniel R. Andersson ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Opioid Receptor ◽  
Stress Reactivity ◽  
Clinical Manifestations ◽  
Preference Test ◽  
Receptor Expression ◽  
Sucrose Preference Test ◽  
Inbred Rat ◽  
Functional Gait

AbstractBack-translating the clinical manifestations of human disease burden into animal models is increasingly recognized as an important facet of preclinical drug discovery. We hypothesized that inbred rat strains possessing stress hyper-reactive-, depressive- or anxiety-like phenotypes may possess more translational value than common outbred strains for modeling neuropathic pain. Rats (inbred: LEW, WKY, F344/ICO and F344/DU, outbred: Crl:SD) were exposed to Spared Nerve Injury (SNI) and evaluated routinely for 6 months on behaviours related to pain (von Frey stimulation and CatWalk-gait analysis), anxiety (elevated plus maze, EPM) and depression (sucrose preference test, SPT). Markers of stress reactivity together with spinal/brain opioid receptor expression were also measured. All strains variously developed mechanical allodynia after SNI with the exception of stress-hyporesponsive LEW rats, despite all strains displaying similar functional gait-deficits after injury. However, affective changes reflective of anxiety- and depressive-like behaviour were only observed for F344/DU in the EPM, and for Crl:SD in SPT. Although differences in stress reactivity and opioid receptor expression occurred, overall they were relatively unaffected by SNI. Thus, anxio-depressive behaviours did not develop in all strains after nerve injury, and correlated only modestly with degree of pain sensitivity or with genetic predisposition to stress and/or affective disturbances.

scholarly journals An experimental study to evaluate the role of aspirin and metformin in prevention of depression in rats

2020 ◽  
Vol 9 (4) ◽  
pp. 605
Author(s):  
Alisha Abbas ◽  
Narendra Kumar ◽  
Sarvesh Singh ◽  
Rahul Kumar ◽  
Akhlaque Ahmad ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Preference Test ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Neurotransmitter System ◽  
Treatment Focus ◽  
Immobility Time ◽  
Current Therapies ◽  
Sucrose Preference Test

Background: Depression was seen to be associated with an increased level of inflammatory biomarkers along with the disturbance in the monoamine neurotransmitter system. Current therapies are mostly focussed on the neurotransmitters imbalance but due to increasing cases of treatment failure there is a need to shift our treatment focus to other potential therapies. This study aimed to evaluate the preventive role of aspirin and metformin in stress induced model of depression in wistar rats.Methods: Fifty four wistar rats were randomly divided into nine groups as normal control, experimental control, aspirin (30 mg/kg, 60 mg/kg), metformin (50 mg/kg, 100 mg/kg), two combination groups and imipramine (15 mg/kg). Depression model was created by the induction of chronic unpredictable mild stress (CUMS) for consecutive 28 days. Behavioural assessment was done by evaluating immobility time in forced swim test (FST) and sucrose preference ratio (SPR) in sucrose preference test. The data were analysed by analysis of variance (ANOVA) test using SPSS software. P<0.05 was considered to be statistically significant.Results: The CUMS led to an increase in immobility time and decrease in SPR. Aspirin and Metformin alone and their combinations showed statistically significant response in preventing the immobility time to increase (p<0.001) and SPR to decrease (p<0.001). However the response of Aspirin was comparable with Imipramine but the response of Metformin was not as significant as of Imipramine (p>0.05).Conclusions: Aspirin and metformin might have a potential role in the prevention of depression.

scholarly journals AMPAkines Have Novel Analgesic Properties in Rat Models of Persistent Neuropathic and Inflammatory Pain

2014 ◽  
Vol 121 (5) ◽  
pp. 1080-1090 ◽  
Author(s):  
Alexander M. Le ◽  
Michelle Lee ◽  
Chen Su ◽  
Anthony Zou ◽  
Jing Wang
Keyword(s):  
Depressive Symptoms ◽  
Nerve Injury ◽  
Ampa Receptors ◽  
Inflammatory Pain ◽  
Forced Swim Test ◽  
Respiratory Drive ◽  
Cold Allodynia ◽  
Glutamate Signaling ◽  
Swim Test ◽  
Forced Swim

Abstract Background: Novel analgesics that do not suppress the respiratory drive are urgently needed. Glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors plays important roles in central pain circuits. AMPAkines augment AMPA receptor function and have been shown to stimulate the respiratory drive to oppose opioid-induced hypoventilation. However, their role in chronic pain states remains unknown. Methods: The authors studied AMPAkines (CX546 and CX516) in rat spared nerve injury (SNI) model of neuropathic pain and Complete Freund’s Adjuvant (CFA) model of inflammatory pain. They measured the effect of AMPAkines on mechanical and cold allodynia. They also evaluated their effect on depressive symptoms of pain using the forced swim test, as time of immobility on this test has been used as a measure for behavioral despair, a feature of depression. Results: The authors found that CX546, compared with dimethyl sulfoxide (DMSO) control, reduced both mechanical and sensory allodynia in SNI (DMSO group, n = 9; CX546 group, n = 11) and CFA models (both DMSO and CX546 groups, n = 9). They found that CX546, compared with control, also reduced depressive symptoms of pain by decreasing immobility on the forced swim test in both SNI (both DMSO and CX546 groups, n = 8) and CFA models (both DMSO and CX546 groups, n = 10). Finally, they found that CX516, compared with control, also reduced mechanical and cold allodynia in the SNI model (both DMSO and CX516 groups, n = 10). Conclusions: AMPAkines alleviate pain hypersensitivity as well as depression-like behavior associated with long-lasting nerve injury and inflammatory insult.

scholarly journals AMPAkines Target the Nucleus Accumbens to Relieve Postoperative Pain

2016 ◽  
Vol 125 (5) ◽  
pp. 1030-1043 ◽  
Author(s):  
Chen Su ◽  
Hau Yeuh Lin ◽  
Runtao Yang ◽  
Duo Xu ◽  
Michelle Lee ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Postoperative Pain ◽  
Nerve Injury ◽  
Ampa Receptors ◽  
Forced Swim Test ◽  
Spared Nerve Injury ◽  
Mechanical Hypersensitivity ◽  
Withdrawal Threshold ◽  
Forced Swim ◽  
Rat Paw

Abstract Background AMPAkines augment the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the brain to increase excitatory outputs. These drugs are known to relieve persistent pain. However, their role in acute pain is unknown. Furthermore, a specific molecular and anatomic target for these novel analgesics remains elusive. Methods The authors studied the analgesic role of an AMPAkine, CX546, in a rat paw incision (PI) model of acute postoperative pain. The authors measured the effect of AMPAkines on sensory and depressive symptoms of pain using mechanical hypersensitivity and forced swim tests. The authors asked whether AMPA receptors in the nucleus accumbens (NAc), a key node in the brain’s reward and pain circuitry, can be a target for AMPAkine analgesia. Results Systemic administration of CX546 (n = 13), compared with control (n = 13), reduced mechanical hypersensitivity (50% withdrawal threshold of 6.05 ± 1.30 g [mean ± SEM] vs. 0.62 ± 0.13 g), and it reduced depressive features of pain by decreasing immobility on the forced swim test in PI-treated rats (89.0 ± 15.5 vs. 156.7 ± 18.5 s). Meanwhile, CX546 delivered locally into the NAc provided pain-relieving effects in both PI (50% withdrawal threshold of 6.81 ± 1.91 vs. 0.50 ± 0.03 g; control, n = 6; CX546, n = 8) and persistent postoperative pain (spared nerve injury) models (50% withdrawal threshold of 3.85 ± 1.23 vs. 0.45 ± 0.00 g; control, n = 7; CX546, n = 11). Blocking AMPA receptors in the NAc with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione inhibited these pain-relieving effects (50% withdrawal threshold of 7.18 ± 1.52 vs. 1.59 ± 0.66 g; n = 8 for PI groups; 10.70 ± 3.45 vs. 1.39 ± 0.88 g; n = 4 for spared nerve injury groups). Conclusions AMPAkines relieve postoperative pain by acting through AMPA receptors in the NAc.

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