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

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.

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EFFECT OF FLAVONE AND ITS MONOHYDROXY DERIVATIVES ON ANIMAL MODELS OF DEPRESSION IN SWISS ALBINO MICE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i2.29856 ◽

2019 ◽

pp. 513-517

Author(s):

SHANMUGAPRIYAN S ◽

JAIKUMAR S ◽

VISWANATHAN S ◽

PARIMALA K ◽

RAJESH M

Keyword(s):

Animal Models ◽

Forced Swim Test ◽

Antidepressant Activity ◽

Tail Suspension Test ◽

Tail Suspension ◽

Swim Test ◽

Forced Swim ◽

Animal Models Of Depression ◽

Pre Treatment ◽

Suspension Test

Objectives: This research was designed to investigate the antidepressant activity of a few structurally related flavones (flavone, 3‑hydroxyflavone, and 7‑hydroxyflavone) and the possible mechanisms involved. Methods: Antidepressant activity was evaluated in mice by subjecting them to forced swim test and tail suspension test. The involvement of adrenergic, serotonergic, nitric oxide (NO), and opioid mechanisms was investigated using suitable interacting chemicals. Results: Flavone, 3‑hydroxyflavone, and 7‑hydroxyflavone exhibited a significant and dose‑dependent reduction in total time of immobility in the forced swim test and tail suspension test. Pre‑treatment with alpha‑methyl‑para‑tyrosine and parachlorophenyl alanine attenuated the reduction in immobility period produced by flavone and its derivatives in forced swim test. Naloxone pre‑treatment partially reversed the effect of flavone while L‑arginine pre‑treatment did not alter their effect. Conclusion: The investigated flavones exhibited promising antidepressant activity in both the animal models of depression. However, the flavone compounds did not alter the motor coordination and ambulatory behavior in the Rotarod and locomotor activity test. The participation of serotonergic, adrenergic, and opioid mechanism in the antidepressant activity of these compounds was elucidated from the results, and the role of NO pathway was excluded.

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

Anesthesiology ◽

10.1097/aln.0b013e31822f16ae ◽

2011 ◽

Vol 115 (4) ◽

pp. 812-821 ◽

Cited By ~ 96

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.

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

Fiziolohichnyĭ zhurnal ◽

10.15407/fz66.05.017 ◽

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.

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Animal Models of Negative Symptoms M100907 Antagonizes PCP-Induced Immobility in a Forced Swim Test in Mice

Neuropsychopharmacology ◽

10.1016/s0893-133x(99)00128-1 ◽

1999 ◽

Vol 21 (6) ◽

pp. S211-S218 ◽

Cited By ~ 29

Author(s):

R Corbett

Keyword(s):

Animal Models ◽

Negative Symptoms ◽

Forced Swim Test ◽

Swim Test ◽

Forced Swim

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The protective effect of L. siceraria against depression using behavioural despair animal models

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20182688 ◽

2018 ◽

Vol 7 (7) ◽

pp. 1391

Author(s):

Karunakar Kota ◽

Sandhya Sharma ◽

P. Ragavendra ◽

Jameela Tahashildar

Keyword(s):

Animal Models ◽

Forced Swim Test ◽

Ethanolic Extract ◽

Antidepressant Activity ◽

Tail Suspension Test ◽

Repeated Treatment ◽

Tail Suspension ◽

Swim Test ◽

Forced Swim ◽

Suspension Test

Background: In recent years, the search for novel pharmacotherapy from medicinal plants for psychiatric illness was significantly progressed. The present study was performed to evaluate the antidepressant activity of ethanolic extract of Lagenaria siceraria in animal models.Methods: The antidepressant activity of ethanolic extract of the fruit of L. siceraria in rats was assessed using forced swim test and tail suspension test. Imipramine at 15 mg/kg was used as standard antidepressant drug.Results: The ethanolic extract of L. siceraria fruit (EELS) was significantly and dose-dependently reduced the duration of immobility after repeated treatment for 7 days in Forced swim test and Tail suspension Test. But combination of L. siceraria (200mg/kg) with Imipramine gave a highly significant result (p<0.001) in reduction of immobility duration and the effect of high dose (400mg/kg) with imipramine (15mg/kg) did not decrease the duration of immobility period in both animal models at end of the study. In this work the dose of 400mg/kg afforded more protection than the imipramine.Conclusions: The results obtained from this study was indicate that the antidepressant activity of L. siseraria.

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