Effect of NMDAR antagonists in the tetrabenazine test for antidepressants: comparison with the tail suspension test

2015 ◽  
Vol 27 (4) ◽  
pp. 228-234 ◽  
Author(s):  
Phil Skolnick ◽  
Tomasz Kos ◽  
Janusz Czekaj ◽  
Piotr Popik

ObjectiveThe N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine, produces rapid and enduring antidepressant effect in patients with treatment-resistant depression. Similar dramatic effects have not been observed in clinical trials with other NMDAR antagonists indicating ketamine may possess unique pharmacological properties. Tetrabenazine induces ptosis (a drooping of the eyelids), and the reversal of this effect, attributed to a sympathomimetic action, has been used to detect first-generation antidepressants, as well as ketamine. Because the actions of other NMDAR antagonists have not been reported in this measure, we examined whether reversal of tetrabenazine-induced ptosis was unique to ketamine, or a class effect of NMDAR antagonists.MethodsThe effects of ketamine and other NMDAR antagonists to reverse tetrabenazine-induced ptosis were examined and compared with their antidepressant-like effects in the tail suspension test (TST) in mice.ResultsAll the NMDAR antagonists tested produced a partial reversal of tetrabenazine-induced ptosis and, as expected, reduced immobility in the TST. Ketamine, memantine, MK-801 and AZD6765 were all about half as potent in reversing tetrabenazine-induced ptosis compared to reducing immobility in the TST, while an NR2B antagonist (Ro 25-6981) and a glycine partial agonist (ACPC) were equipotent in both tests.ConclusionThe ability to reverse tetrabenazine-induced ptosis is a class effect of NMDAR antagonists. These findings are consistent with the hypothesis that the inability of memantine, AZD6765 (lanicemine) and MK-0657 to reproduce the rapid and robust antidepressant effects of ketamine in the clinic result from insufficient dosing rather than a difference in mechanism of action among these NMDAR antagonists.

Author(s):  
Ajoy Borah ◽  
Binita Singha ◽  
Swopna Phukan

Objective: Depression is a major psychiatric disorder affecting nearly 350 million people worldwide and imposes a substantial health burden on the society. Ceftriaxone has demonstrated neuroprotective effects in animals. It has also undergone trials as a treatment option for amyotrophic lateral sclerosis. This study was therefore undertaken to evaluate the antidepressant-like effect of ceftriaxone in mice.Methods: Ceftriaxone was administered at three different doses (0.130, 0.195 and 0.260g/kg) to Swiss albino mice of either sex by intra peritoneal (i. p.) route. The period of immobility in control and drug-treated mice were recorded in forced swimming test (FST) and tail suspension test (TST). The antidepressant effect of ceftriaxone indicated by the decrease in duration of immobility was compared to that of fluoxetine (0.020 g/kg, i. p.).Results: Ceftriaxone decreased the duration of immobility in mice. It showed a significant dose-dependent antidepressant effect. The antidepressant effect of 0.260g/kg of ceftriaxone was comparable to that of fluoxetine in the TST but not in the FST.Conclusion: The results of the present study indicate antidepressant activity of Ceftriaxone. The study shows that ceftriaxone has additional action on the central nervous system other than neuroprotection. Ceftriaxone therapy in cases of encephalomeningitis and in various cases of hemorrhages in the brain can, therefore, prevent the development of depression in future


2019 ◽  
pp. 01-12
Author(s):  
Rui Li ◽  
Wai-Kin Mat ◽  
Wing-Man Chan ◽  
T Yiu-Cheong Ho ◽  
Rigil K Yeung ◽  
...  

The racemate dl-tetrahydropalmatine (dl-THP) is known for its analgesic and sedative effects, and has been shown by us to be a potential agent for the treatment of anxiety.Herein, to delineate the therapeutic potentials of its different isomeric forms, the behavioral effects of l-THP, dl-THP and d-THP were compared regarding their anxiolytic and antidepressant properties in mouse behavioral models using the elevated plus-maze test and tail suspension test respectively. The anxiolytic and antidepressant effects of both l-THP and dl-THP were evident in forty-five minutes following oral administration. Moreover, l-THP exhibited much greater anxiolytic potency in the elevated plus-maze (0.1-2.5 mg/kg) and antidepressant potency in the tail suspension test (0.5-5.0 mg/kg) than dl-THP, whereas d-THP was inactive in either of these tests. As well, l-THP enhanced sociability and preference for social novelty at 0.1-0.5 mg/kg in Crawley’s three-chamber behavioral tests, and inhibited the amphetamine-induced manic-like hyperactivity of amphetamine-sensitized mice at 0.05-0.2 mg/kg. These pharmacological actions of l-THP were unaccompanied by any significant locomotor or myorelaxant side-effects. Co-administration of flumazenil, a GABAA receptor antagonist, inhibited the anxiolytic and antidepressant effects of l-THP, even though the binding affinity of l-THP was higher for dopamine D2-like receptors than for GABAA receptors. On this basis, l-THP displayed potential as a fast-acting drug for the treatment of anxiety, depression and bipolar disorder. Keywords: l-THP; dl-THP; Anxiolysis; Antidepressant; GABAA receptor; Fast-acting


Author(s):  
Chiranjeevi Bonda ◽  
Sudhir Pawar ◽  
Jaisen Lokhande

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.


2009 ◽  
Vol 92 (3) ◽  
pp. 465-468 ◽  
Author(s):  
Daisy Carbajal ◽  
Yazmin Ravelo ◽  
Vivian Molina ◽  
Rosa Mas ◽  
María de Lourdes Arruzazabala

Author(s):  
Rajiv Kumar ◽  
Hansraj Kumar ◽  
U. S. P. Keshri ◽  
Manju Gari

Background: Depression is a common psychiatric illness but conventional antidepressants are often shows unpredictable response. Pharmacological profiles of many atypical antipsychotics have potential antidepressant effect. Ziprasidone is an atypical antidepressant with 5HT1A agonistic activity and 5HT1D, 5HT2A and D2 receptors antagonistic activity. It’s a potential candidate for evaluating possible antidepressant activity.Methods: Behavioural despair test are widely used for evaluation of potential antidepressant molecule. Tail suspension test is a variant of behavioural despair test. Healthy male Wistar albino rat 18 in number and weighing between of 150-200 grams were divided in 3 groups with 6 rats in each group. Group A was treated with 0.9% Normal Saline, Group B with Fluoxetine and Group C with Ziprasidone for 28 days. Tail suspension test was done on day 0, 7, 14, 21 and 28 days.Results: In comparison to Normal saline both the drugs shows significant antidepressant activity after 28 days of treatment. While antidepressant activity of fluoxetine started to appear from day 7; that of ziprasidone started to appear from 14th day.Conclusions: Ziprasidone can be suitable candidate for clinical trials of Major Depressive Disorders not responding to conventional antidepressant. 


Author(s):  
Igor Kumburovic ◽  
Davor Kumburovic ◽  
Sanja Vujovic ◽  
Zlata Rajkovic ◽  
Stefan Velickovic

Abstract In order to evaluate the effects of Satureja hortensis L. extract on cisplatin-induced behavioral alterations in the tail suspension test (TST), we included 35 male Wistar albino rats in this study, divided into 7 equal groups. Cisplatin was administered (single dose of 7.5 mg/kg, i.p., on the fifth day) alone, and in groups with orally administered (for 10 days) Satureja hortensis L. extract (50, 100, and 200 mg/kg), and silymarin (100 mg/kg) in individual groups. The behavioral testing was performed in TST, and the following parameters were obtained: the latency to the first immobility, the number of immobility episodes, and the total duration of immobility. Cisplatin application increased the latency to the first immobility, but decreased the number of immobility episodes and the total duration of immobility. Oral administration of Satureja hortensis L. extract in a dose of 100 mg/kg attenuated cisplatin-induced alterations, and those effects were similar to silymarin group. The extract in a dose of 200 mg/kg diminished cisplatin-induced effect only for the total duration of immobility, while in a dose of 50 mg/kg, the extract had no impact on cisplatin effects. Although common use of this methodology would lead to a conclusion that cisplatin produced antidepressant effect, comparison with certain literature data allows the conclusion that this action of cisplatin may be attributed to its anxiogenic action that was attenuated by antioxidant supplementation (Satureja hortensis L.) in an adequate dose (100 mg/kg).


Author(s):  
Anki Tyagi ◽  
Vaibhav Walia

ABSTRACTAim: To determine the effect of gender difference in the antidepressant effect of fluoxetine (FLX) in mice in tail suspension test (TST).Methods: Swiss albino mice of either sex were used and the depression-like behavior was measured by TST.Results: The present study showed that there was a significant difference in the immobility period of male mice and female mice in TST. However, theantidepressant effect of FLX differs significantly in male mice and female mice in TST.Conclusion: It has been concluded that the antidepressant effect of FLX in TST was affected by the gender difference as suggested by the results ofthe present study.Keywords: Depression, Estrogen, Female, Fluoxetine, Mice, Serotonin.


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