Effects of single and combined gabapentin use in elevated plus maze and forced swimming tests

2014 ◽  
Vol 26 (5) ◽  
pp. 307-314 ◽  
Author(s):  
Fatma Sultan Kilic ◽  
Sule Ismailoglu ◽  
Bilgin Kaygisiz ◽  
Setenay Oner

BackgroundGabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders.ObjectivesWe aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats.Material and MethodsFemale Spraque–Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively.ResultsIt was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them.ConclusionsThese data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Harquin Simplice Foyet ◽  
David Emery Tsala ◽  
Armand Abdou Bouba ◽  
Lucian Hritcu

The present study examined the anxiolytic and antidepressant effects of the aqueous extract ofAlafia multiflora Stapf(AM) stem barks (150 and 300 mg/kg, 7 days administration) on rats and mice, using experimental paradigms of anxiety and depression. In the open field, the aqueous extract increased significantly the number of center square crossed and the time spent at the center of the field as well as the rearing time, while the grooming time was reduced significantly. In the elevated plus maze, the aqueous extract increased the time spent and the number of entries in the open arms. All these effects were also completely reversed by flumazenil, an antagonist of benzodiazepine receptors and pindolol aβ-adrenoceptors blocker/5-HT 1A/1B receptor antagonist. The time spent in the light compartment, the latency time, and the number of the light-dark transitions increased significantly in the light/dark exploration test after the treatment with AM. The extract was able to reduce significantly the immobility time and increase swimming as well as climbing duration. Taken together, the present work evidenced anxiolytic effects of the aqueous extract of AM that might involve an action on benzodiazepine-type receptors and an antidepressant effect where noradrenergic mechanisms will probably play a role.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jian Li ◽  
Qian-tong Liu ◽  
Yi Chen ◽  
Jie Liu ◽  
Jin-li Shi ◽  
...  

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.


2021 ◽  
Author(s):  
Siamak Shahidi ◽  
Asghar Dindar ◽  
Alireza Komaki ◽  
Reihaneh Sadeghian

Abstract ObjectiveAnxiety behavior is regulated by different neurotransmitter systems. There has been no direct relationship between endocannabinoid and cholinergic systems on anxiety in previous studies. This study investigated the effects of each of these systems separately and simultaneously using Donepezil (Cholinesterase inhibitor) and URB-597 (endocannabinoid degrading enzyme inhibitor) on anxiety-like behavior. MethodEighty-eight male mice were divided into eleven groups (n=8) including control (saline), diazepam (0.3 mg /kg), URB-597 (0.1, 0.3, or 1 mg /kg), donepezil (0.5, 1 or 2 mg/kg) and the combination of the two drugs at low, medium and high doses. All treatments were injected intraperitoneally 30 minutes before the elevated plus maze test. ResultsSeparate administration of URB597, donepezil or diazepam increased the number and time spent of open arms compared to the control group. Concurrent administration of URB and donepezil at low, medium and high doses did not change the number of open arms entries compared to the control group, but they reduced the number of entries to the closed arms. ConclusionsThese results suggest that strengthening any cholinergic or endocannabinoid system has anxiolytic effect similar to diazepam. However, the interaction of these two systems has fewer anxiolytic effects compared to the effects of each alone. It seems that these drugs alone may represent a strategy for the treatment of anxiety disorders.


Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 892 ◽  
Author(s):  
Rade Vukovic ◽  
Igor Kumburovic ◽  
Jovana Joksimovic Jovic ◽  
Nemanja Jovicic ◽  
Jelena S. Katanic Stankovic ◽  
...  

Since cisplatin therapy is usually accompanied with numerous toxicities, including neurotoxicity, that involve tissue oxidative damage, the aim of this study was to evaluate the possible protective effect of N-acetylcysteine (NAC) on the anxiogenic response to cisplatin (CIS). Thirty-two male Wistar albino rats divided into four groups (control, cisplatin, NAC, and CIS + NAC). All treatments were delivered intraperitoneally. On day one, the control and cisplatin groups received saline while the NAC and CIS + NAC groups were administered with NAC (500 mg/kg). On the fifth day, the control group received saline while the CIS group was treated with cisplatin (7.5 mg/kg), the NAC group again received NAC (500 mg/kg), and the CIS + NAC group was simultaneously treated with cisplatin and NAC (7.5 and 500 mg/kg, respectively). Behavioral testing, performed on the tenth day in the open field (OF) and elevated plus maze (EPM) tests, revealed the anxiogenic effect of cisplatin that was significantly attenuated by NAC. The hippocampal sections evaluation showed increased oxidative stress (increased lipid peroxidation and decline in antioxidant enzymes activity) and proapoptotic action (predominantly by diminished antiapoptotic gene expression) following a single dose of cisplatin. NAC supplementation along with cisplatin administration reversed the prooxidative and proapoptotic effects of cisplatin. In conclusion, the results obtained in this study confirmed that antioxidant supplementation with NAC may attenuate the cisplatin-induced anxiety. The mechanism of anxiolytic effect achieved by NAC may include the decline in oxidative damage that down regulates increased apoptosis and reverses the anxiogenic action of cisplatin.


2018 ◽  
Vol 19 (11) ◽  
pp. 3468 ◽  
Author(s):  
Shuai Wang ◽  
Canhong Wang ◽  
Zhangxin Yu ◽  
Chongming Wu ◽  
Deqian Peng ◽  
...  

In our previous investigation, we found that agarwood essential oil (AEO) has a sedative-hypnotic effect. Sedative-hypnotic drugs usually have an anxiolytic effect, where concomitant anxiety and depression are a common comorbidity. Therefore, this study further investigated the anxiolytic and antidepressant effects of AEO using a series of animal behavior tests on a restraint stress-induced mice model. The elevated plus maze (EPM) test, the light dark exploration (LDE) test, and the open field (OF) test demonstrated that AEO has a significant anxiolytic effect. Simultaneously, the tail suspension (TS) test and the forced swimming (FS) test illuminated that AEO has an antidepressant effect with the immobility time decreased. Stress can cause cytokine and nitric oxide (NO) elevation, and further lead to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. AEO was shown to dose-dependently inhibit the levels of cytokines, including interleukin 1α (IL-1α), IL-1β, and IL-6 in serum, significantly decrease the mRNA level of neural nitric oxide synthase (nNOS) in the cerebral cortex and hippocampus, and inhibit the nNOS protein level in the hippocampus. Concomitant measurements of the HPA axis upstream regulator corticotropin releasing factor (CRF) and its receptor CRFR found that AEO significantly decreases the gene expression of CRF, and significantly inhibits the gene transcription and protein expression of CRFR in the cerebral cortex and hippocampus. Additionally, AEO dose-dependently reduces the concentrations of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) downstream of the HPA axis, as measured by ELISA kits. These results together demonstrate that AEO exerts anxiolytic and antidepressant effects which are related to the inhibition of CRF and hyperactivity of the HPA axis.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Long Cheng ◽  
Guo-feng Pan ◽  
Xiao-bo Sun ◽  
Yun-xiang Huang ◽  
You-shun Peng ◽  
...  

There are few studies on the neuropharmacological properties of asparagus, which was applied in Chinese traditional medicine as a tonic and heat-clearing agent. The present study was designed to investigate the anxiolytic-like activity of the aqueous extract of asparagus stem (AEAS) using elevated plus maze (EPM) and Vogel conflict tests (VCT) in mice. AEAS significantly increased the percentage of time spent in open arms in EPM, when compared with control group. In the Vogel conflict drinking test, the numbers of punished licks increased to 177% and 174% by the treatment of AEAS at the doses of 1.5 and 3.0 g/kg (250 and 500 mg sarsasapogenin per kilogram of body weight), compared with control group. The serum cortisol level decreased significantly, at the same time. In conclusion, these findings indicated that the aqueous extract of asparagus stem exhibited a strong anxiolytic-like effect at dose of 1.5 and 3.0 g/kg (250 and 500 mg sarsasapogenin per kilogram of body weight) in experimental models of anxiety and may be considered an alternative approach for the management of anxiety disorder.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Foyet Harquin Simplice ◽  
Tsala David Emery ◽  
Ngatanko Abaissou Hervé Hervé

We evaluated the anxiolytic and antidepressant effects of the aqueous extract of the bark ofTapinanthus dodoneifolius(TAE) (Danser) (25, 50, and 100 mg/kg), using open field, elevated plus maze, and forced swimming tests. Effect of TAE was compared to standard drugs diazepam (2 mg/kg) and imipramine (10 mg/kg). Additionally, the same doses of TAE were evaluated on rat's memory using Y-maze task. Results showed a significant (P<0.05; 100 mg/kg) increase in the percentage of open arm entry and the time spent in the open arms in the elevated plus maze, suggesting an anxiolytic activity of the extract. In a dose-dependant manner, TAE at 25 mg/kg significantly (P<0.05) decreased the number of lines crossed and the rearing behavior in the open field test, suggesting its possible sedative activity. In the forced swimming test, the immobility time of the animal was significantly reduced (P<0.05) by TAE (100 mg/kg), compared to control, and this effect was quite comparable to that of imipramine. In the Y-maze paradigm, TAE at 50 mg/kg caused a significant increase in the spontaneous alternations but with a significant decrease in exploratory behavioral pattern. Taking these results together, TAE improved the spatial memory and showed anxiolytic, antidepressant, and sedative activities. The present results support the anxiolytic and antidepressant activities of TAE and, to our knowledge, for the first time, demonstrate its enhancing effect on memory.


2019 ◽  
Vol 14 (5) ◽  
pp. 1934578X1984635
Author(s):  
Nai-Wen Tsao ◽  
Wei-Wen Cheng ◽  
Yen-Hsueh Tseng ◽  
Sheng-Yang Wang

Alpinia pricei Hayata (Zingiberaceae) is a spicy plant endemic to Taiwan. In this study, several behavioral analyses were used to evaluate the neuropharmacological activity of A. pricei in mice. Oral administration of 100, 300, and 500 mg/kg of A. pricei extract (APE) significantly prolonged pentobarbital-induced sleeping time in mice by 24.5%, 74.7%, and 79.0%, respectively. Also, the antidepressant effect of APE was evaluated using suspended tail and forced swimming tests. The immobility periods of mice in the suspended tail and forced swimming tests were reduced after the administration of APE. Further, an elevated plus-maze test was used to study the anxiolytic activity of APE. After treatment with 500 mg/kg of APE the time the mice spent in the open arms (31.55 ± 13.65 seconds) and the number of times they entered the open arms (51.75 ± 16.51 times) ( P < 0.05) of the plus-maze increased significantly compared to a saline-treated group. Our results also revealed that APE showed potent analgesic activity in the tail-flick test; all dosages of APE prolonged the tail-flick time for up to 90 minutes. In conclusion, APE had a potent effect on the neuropharmacological activities of mice. Finally, the main compounds of APE were separated, and spectral analysis was conducted. The major constituents of APE were characterized as 5,7-dimethoxyflavanone (1), desmethoxyyangonin (2), 2′,4′,6′-trimethoxychalcone (3), cardamonin (4), trans/ cis-3,5-dimethoxystilbene (5), and flavokawain B (6).


Author(s):  
Suhera M. Aburawi ◽  
Sumaya A. Baayo

Depression is a major cause of morbidity worldwide. Fluoxetine is a selective serotonin reuptake inhibitor, and is effective antidepressant medication. Selenium is essential for good health but required only in small amounts.Aim of the study is to investigate the effects of fluxetine alone and in presence of selenium on anxiety, spontaneous motor activity and antidepressant behavior. Also, the study aims to investigate the effects of selenium on spontaneous motor activity, anxiety measure, and antidepressant behavior, using photoelectric cells, elevated plus maze and forced swimming maze.Mice were divided into 5 group (n=6). Group 1 (control), administered 1% tween 80 (5 ml/kg); group 2 administered selenium (200 µg/kg); group 3 received diazepam as a positive control (1 mg/kg); group 4 received fluoxetine (20 mg/kg); while group 5 received combined treatment of fluoxetine and selenium. All drugs injected sub acutely (three doses), mice were intraperitoneally administered at 24, 5, and 1.0 hrs before scoring. All drugs administered as suspension in 1% Tween 80 (T80). It was injected in volume 5ml/kg. Plus maze, photoelectric cells and forced swimming maze models were used.Fluoxetine has no effect on anxiety or locomotor activity; while selenium produced anxiolytic effect without changes on locomotor activity. Fluoxetine has antidepressant activity without any effect on duration of climbing. Selenium induced antidepressant effect with climbing action. Fluoxetine abolish the anxiolytic effect of selenium when administered together, but the combined treatment decreases the locomotor activity. Fluoxetine administration with selenium counteract the antidepressant effect of each other and climbing effect of selenium. Finally, selenium improves anxiety and depression behavior in albino mice, and might be used as an alternative therapy instead of fluoxetine (which treat antidepression only); but it must not be taken in combination with it.


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