Antagonism of non-NMDA receptors in the dorsal periaqueductal grey induces anxiolytic effect in the elevated plus maze

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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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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Anxiolytic effect of clonazepam in female rats: Grooming microstructure and elevated plus maze tests

European Journal of Pharmacology ◽

10.1016/j.ejphar.2012.03.038 ◽

2012 ◽

Vol 684 (1-3) ◽

pp. 95-101 ◽

Cited By ~ 22

Author(s):

Maurício S. Nin ◽

Natividade S. Couto-Pereira ◽

Marilise F. Souza ◽

Lucas A. Azeredo ◽

Marcelo K. Ferri ◽

...

Keyword(s):

Elevated Plus Maze ◽

Anxiolytic Effect ◽

Female Rats ◽

Plus Maze

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Nicotine-induced anxiogenic-like behaviours of rats in the elevated plus-maze: possible role of NMDA receptors of the central amygdala

Journal of Psychopharmacology ◽

10.1177/0269881111412094 ◽

2011 ◽

Vol 26 (4) ◽

pp. 555-563 ◽

Cited By ~ 14

Author(s):

Mohammad Reza Zarrindast ◽

Arash Aghamohammadi-Sereshki ◽

Ameneh Rezayof ◽

Parvin Rostami

Keyword(s):

Locomotor Activity ◽

Nmda Receptor ◽

Nmda Receptors ◽

Elevated Plus Maze ◽

Nmda Receptor Antagonist ◽

Central Amygdala ◽

Receptor System ◽

Plus Maze ◽

Male Wistar Rats

The objective of the present study was to investigate the possible role of the N-methyl-D-aspartate (NMDA) receptor system of the central amygdala (CeA) in the anxiogenic-like effect of nicotine. Male Wistar rats with cannulas aimed to the CeA were submitted to the elevated plus-maze (EPM). Intraperitoneal (i.p.) injections of nicotine (0.6 and 0.8 mg/kg) decreased percentage open arm time spent (%OAT) and percentage open arm entries (%OAE), but not locomotor activity, indicating an anxiogenic-like response. Bilateral intra-CeA microinjection of NMDA (0.005–0.1 μ g/rat) decreased %OAT, but not %OAE and locomotor activity. Moreover, intra-CeA microinjection of NMDA (0.05 μ g) with an ineffective dose of nicotine (0.4 mg/kg, i.p.) reduced %OAT and %OAE without effect on locomotor activity. On the other hand, intra-CeA microinjection of the NMDA receptor antagonist D-AP5 (0.05–0.5 μ g/rat) increased both %OAT and %OAE, showing an anxiolytic-like effect of the drug. Co-administration of the same doses of D-AP5 with nicotine (0.6 mg/kg, i.p.) increased %OAT and %OAE, but not locomotor activity. Intra-CeA microinjection of D-AP5 reversed the response induced by NMDA (0.1 μ g/rat) in the EPM. The results may support the possible involvement of glutamate transmission, through NMDA receptors of central amygdala in the anxiogenic-like effect of nicotine in the EPM task.

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