The anxiolytic effect of salicylic acid is mediated via the GABAergic system in the fear potentiated plus maze behavior in rats

Abstract Salicylic acid (SA) is a natural phenolic compound in plants with many beneficial effects for humans. The anxiolytic effect of this compound has been reported in animal models, but its mechanism of action remains unclear. In this study, by using the fear potentiated plus maze test, we evaluated the effect of salicylic acid on the gene expression of the main form of GABA synthesizing enzyme i.e., the enzyme glutamic acid decarboxylase 67 (GAD67), in the ventral subiculum of the hippocampus. Also, the hypnotic effect of Salicylic acid was evaluated. Animals were divided into the solvent, (SA) and diazepam treated groups (n = 6). For evaluating the anxiolytic effect of Salicylic acid, animals were subjected to 2 hours of isolation, before placing them in the elevated plus maze (EPM). Afterward, the ventral part of the hippocampus was removed for evaluating the change in (GAD67) gene expression by the reverse transcription-quantitative polymerase chain reaction (RTqPCR) technique. The hypnotic effect of Salicylic acid was evaluated in the ketamine induced sleeping test. Our results showed that Salicylic acid at 10, 30 (mg/kg) increased time spent and entries to the open arms in the (EPM) (p < 0.05). (RTqPCR) revealed that 30mg/kg of Salicylic acid increased (GAD67) gene expression (p < 0.001). Salicylic acid (30 and 300 mg/kg) also increased the duration of sleep, in ketamine induced sleeping test (p < 0.05). Our results showed that Salicylic acid has anxiolytic and hypnotic effects and it exerts its anxiolytic effect partly, via up regulation of (GAD67) in the ventral part of the hippocampus.

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Effects of Simultaneous Reinforcement of Endocannabinoid and Cholinergic Systems on Anxiety-Like Behavior in Mice

10.21203/rs.3.rs-422248/v1 ◽

2021 ◽

Author(s):

Siamak Shahidi ◽

Asghar Dindar ◽

Alireza Komaki ◽

Reihaneh Sadeghian

Keyword(s):

Elevated Plus Maze ◽

Enzyme Inhibitor ◽

Endocannabinoid System ◽

Anxiolytic Effect ◽

Control Group ◽

Concurrent Administration ◽

Elevated Plus Maze Test ◽

Cholinergic Systems ◽

Plus Maze ◽

High Doses

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.

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Low frequency deep brain stimulation in the inferior colliculus ameliorates haloperidol-induced catalepsy and reduces anxiety in rats

PLoS ONE ◽

10.1371/journal.pone.0243438 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243438

Author(s):

Hannah Ihme ◽

Rainer K. W. Schwarting ◽

Liana Melo-Thomas

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Low Frequency ◽

Anxiolytic Effect ◽

Motor Deficits ◽

Sham Treatment ◽

Plus Maze ◽

Aversive Behavior ◽

The Brain ◽

Deep Brain

Deep brain stimulation (DBS) of the colliculus inferior (IC) improves haloperidol-induced catalepsy and induces paradoxal kinesia in rats. Since the IC is part of the brain aversive system, DBS of this structure has long been related to aversive behavior in rats limiting its clinical use. This study aimed to improve intracollicular DBS parameters in order to avoid anxiogenic side effects while preserving motor improvements in rats. Catalepsy was induced by systemic haloperidol (0.5mg/kg) and after 60 min the bar test was performed during which a given rat received continuous (5 min, with or without pre-stimulation) or intermittent (5 x 1 min) DBS (30Hz, 200–600μA, pulse width 100μs). Only continuous DBS with pre-stimulation reduced catalepsy time. The rats were also submitted to the elevated plus maze (EPM) test and received either continuous stimulation with or without pre-stimulation, or sham treatment. Only rats receiving continuous DBS with pre-stimulation increased the time spent and the number of entries into the open arms of the EPM suggesting an anxiolytic effect. The present intracollicular DBS parameters induced motor improvements without any evidence of aversive behavior, pointing to the IC as an alternative DBS target to induce paradoxical kinesia improving motor deficits in parkinsonian patients.

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Evaluation of anxiolytic and hypoglycemic potential of Cissus adnata Roxb. in animal model

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2018-0130 ◽

2019 ◽

Vol 17 (2) ◽

Author(s):

Mohammed Shamim Hasan ◽

Md. Giash Uddin ◽

Mohammed Shoibe ◽

Abdullah Al Mahmud ◽

Sujan Banik

Keyword(s):

Glucose Tolerance Test ◽

Methanolic Extract ◽

Anxiolytic Effect ◽

Tolerance Test ◽

Mice Model ◽

Board Test ◽

Plus Maze ◽

Hole Board ◽

Phytochemical Constituents ◽

Hole Board Test

AbstractBackgroundThis study was designed to evaluate the anxiolytic and hypoglycemic potential of methanolic extract of Cissus adnata Roxb. is a crucial medicinal plant used in many disorders belongs to Vitaceae family.MethodsElevated plus maze (EPM) test and hole board test was applied for the anxiolytic activity with the Swiss albino mice. The hypoglycemic activity was measured by the glucose tolerance test in mice model. The capacity to produce the desired effect of the plant extract (200 and 400 mg/kg) was compared with the anxiolytic drug of standard diazepam (1 mg/kg i.p.) and anti-diabetic drug glibenclamide (10 mg/kg i.p.), respectively.ResultsThe phytochemical screening of Cissus adnata extract exposed the presence of carbohydrate, phenol, flavonoid, saponins, cardiac glycoside, tannin, and gum. The anxiolytic effect was detected in both experiments which significantly raised the number of head dips and the time spent in the open arm of the EPM (p<0.05) as the dose enlarged. Hypoglycemic study of the extracts shows better effect by reducing blood glucose level.ConclusionsThe better anxiolytic and hypoglycemic activities in the present study are due to the existence of various phytochemical constituents like saponins, flavonoids, terpenoids, phenols, and tannins in this methanolic extract.

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Chemical Composition of Essential Oil from Flower of ‘Shanzhizi’ (Gardenia jasminoides Ellis) and Involvement of Serotonergic System in Its Anxiolytic Effect

Molecules ◽

10.3390/molecules25204702 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4702

Author(s):

Nan Zhang ◽

Mu Luo ◽

Lei He ◽

Lei Yao

Keyword(s):

Essential Oil ◽

Elevated Plus Maze ◽

Anxiolytic Effect ◽

Serotonergic System ◽

Control Treatment ◽

Monoamine Neurotransmitters ◽

Neurotransmitter Receptor ◽

Gardenia Jasminoides ◽

Plus Maze ◽

Gardenia Jasminoides Ellis

Gardenia jasminoides Ellis is a famous fragrant flower in China. Previous pharmacological research mainly focuses on its fruit. In this study, the essential oil of the flower of ‘Shanzhizi’, which was a major variety for traditional Chinese medicine use, was extracted by hydro distillation and analyzed by GC-MS. Mouse anxiety models included open field, elevated plus maze (EPM), and light and dark box (LDB), which were used to evaluate its anxiolytic effect via inhalation. The involvement of monoamine system was studied by pretreatment with neurotransmitter receptor antagonists WAY100635, flumazenil and sulpiride. The monoamine neurotransmitters contents in the prefrontal cortex (PFC) and hippocampus after aroma inhalation were also analyzed. The results showed that inhalation of G. jasminoides essential oil could significantly elevated the time and entries into open arms in EPM tests and the time explored in the light chamber in LDB tests with no sedative effect. WAY100635 and sulpiride, but not flumazenil, blocked its anxiolytic effect. Inhalation of G. jasminoides essential oil significantly down-regulated the 5-HIAA/5-HT in the PFC and reduced the 5-HIAA content in hippocampus compared to the control treatment. In conclusion, inhalation of gardenia essential oil showed an anxiolytic effect in mice. Monoamine, especially the serotonergic system, was involved in its anxiolytic effect.

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

Acta Neuropsychiatrica ◽

10.1017/neu.2014.17 ◽

2014 ◽

Vol 26 (5) ◽

pp. 307-314 ◽

Cited By ~ 4

Author(s):

Fatma Sultan Kilic ◽

Sule Ismailoglu ◽

Bilgin Kaygisiz ◽

Setenay Oner

Keyword(s):

Elevated Plus Maze ◽

Anxiolytic Effect ◽

Experimental Models ◽

Forced Swimming ◽

Anxiety And Depression ◽

Antidepressant Effect ◽

Control Group ◽

Psychiatric Illnesses ◽

Plus Maze ◽

Antidepressant Effects

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.

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Absence of sibutramine effect on spontaneous anxiety in rats

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302010000400006 ◽

2010 ◽

Vol 54 (4) ◽

pp. 375-380 ◽

Cited By ~ 7

Author(s):

Silvana S. Frassetto ◽

Isis O. Alves ◽

Marislane M. Santos ◽

Ana E. S. Schmidt ◽

Janaína J. Lopes ◽

...

Keyword(s):

Chronic Treatment ◽

Elevated Plus Maze ◽

Anxiolytic Effect ◽

Chronic Administration ◽

Positive Control ◽

Maximum Effect ◽

Plus Maze ◽

The Central Nervous System ◽

Treatment Of Obesity ◽

Acute And Chronic Treatments

INTRODUSTION: Sibutramine has been described as a drug recommended for treatment of obesity, since it has the ability to inhibit the reuptake of serotonin and noradrenaline in the central nervous system, thereby increasing energy expenditure. OBJECTIVE: Investigate the anxiogenic and anxiolytic effects of acute and chronic treatment with sibutramine in rats submitted to the task of the elevated plus-maze. METHODS: Diazepam was used as a positive control for the anxiolytic effect, and the task of the elevated plus-maze showed sensitivity to detect the effect. In the chronic treatment, sibutramine was ingested for a period of two months. RESULTS: The acute and chronic treatments at the studied dose, which is described to produce a maximum effect of anti-obesity in rats, did not interfere with anxiety. CONCLUSIONS: The acute and chronic administration of sibutramine is not related to anxiolytic or anxiogenic effects.

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