Neuropharmacological Activity of the New Piperazine Derivative 2-(4-((1- Phenyl-1H-Pyrazol-4-yl)Methyl)Piperazin-1-yl)Ethyl Acetate is Modulated by Serotonergic and GABAergic Pathways

2021 ◽  
Vol 20 ◽  
Author(s):  
Lorena de Souza Almeida ◽  
Ianca Gontijo Cavalcante Santana ◽  
Lorrane Kelle da Silva Moreira ◽  
Larissa Córdova Turones ◽  
Germán Sanz ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Gabaa Receptor ◽  
Serotonergic System ◽  
Anxiety And Depression ◽  
Pharmacological Treatments ◽  
Design Synthesis ◽  
Plus Maze ◽  
Way 100635 ◽  
Swimming Test ◽  
Benzodiazepine Site

Background: Pharmacological treatments for mental disorders, such as anxiety and depression, present several limitations and adverse effects. Therefore, new pharmacotherapy with anxiolytic and antidepressant potential is necessary, and the study of compounds capable of interacting with more than one pharmacological target may provide new therapeutic options. Objectives: In this study, we proposed the design, synthesis of a new compound, 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethyl acetate (LQFM192), pharmacological evaluation of its anxiolytic-like and antidepressant-like activities, as well as the possible mechanisms of action involved. Methods: Administration of LQFM192 was carried out prior to the exposure of male Swiss mice to behavioral tests, such as the elevated plus-maze and forced swimming test. The involvement of the serotonergic system was studied by pretreatment with WAY-100635 or p-chlorophenylalanine (PCPA) and the involvement of the benzodiazepine site of the GABAA receptor by pretreatment with flumazenil. Results: The treatment with LQFM192 at doses of 54 and 162 µmol/kg demonstrated anxiolyticlike activity that was blocked by WAY-100635, PCPA, and flumazenil pretreatments. The potential antidepressant-like activity was visualized at the same doses and blocked by WAY-100635 and PCPA. Conclusion: In summary, the anxiolytic-like activity of LQFM192 is mediated by the serotonergic system and the benzodiazepine site of the GABAA receptor, and the antidepressant-like activity through the serotonergic system.

scholarly journals Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats

2015 ◽  
Vol 73 (2) ◽  
pp. 132-139 ◽  
Author(s):  
Hamid Azizi-Malekabadi ◽  
Masoume Pourganji ◽  
Hoda Zabihi ◽  
Mohsen Saeedjalali ◽  
Mahmoud Hosseini
Keyword(s):  
Sham Group ◽  
Forced Swimming Test ◽  
Elevated Plus Maze ◽  
Ovarian Hormones ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Anxiety And Depression ◽  
Ovarian Hormone ◽  
Plus Maze ◽  
Swimming Test

The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.

Anxiolytic- and antidepressant-like effects of angiotensin-(1–7) in hypertensive transgenic (mRen2)27 rats

2016 ◽  
Vol 130 (14) ◽  
pp. 1247-1255 ◽  
Author(s):  
Ana Flávia Almeida-Santos ◽  
Lucas M. Kangussu ◽  
Fabrício A. Moreira ◽  
Robson A.S. Santos ◽  
Daniele C. Aguiar ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Enzyme Treatment ◽  
Anxiety And Depression ◽  
Sprague Dawley ◽  
Intracerebroventricular Infusion ◽  
Sprague Dawley Rats ◽  
Plus Maze ◽  
Swimming Test ◽  
Pre Treatment ◽  
G Protein Coupled

Angiotensin-(1–7) [Ang-(1–7)], a counter-regulatory peptide of the renin–angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain. Ang-(1–7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioural responses. In the present study we tested the hypothesis that Ang-(1–7) could attenuate the anxiety- and depression-like behaviours observed in transgenic hypertensive (mRen2)27 rats (TGRs). We also hypothesized that Ang-(1–7) could be involved in the anxiolytic-like effect induced by ACE (angiotensin-converting enzyme) treatment in these hypertensive rats. Therefore, TGRs and Sprague–Dawley rats were subjected to the Elevated Plus Maze (EPM) test, Forced Swimming Test (FST) and Novelty Suppressed Feeding (NSF). TGRs presented a decreased percentage of entries in the open arms of the EPM test, a phenotype reversed by systemic treatment with enalapril or intracerebroventricular infusion of Ang-(1–7). It is interesting that pre-treatment with A779, a selective Mas receptor antagonist, prevented the anxiolytic-like effect induced by the ACE inhibitor. In the NSF test, TGRs showed increased latency to eating, an indicative of a higher aversion in response to a new environment. These animals also showed increased immobility in the FST. Again, Ang-(1–7) reversed this phenotype. Thus, our data showed that Ang-(1–7) can modulate anxiety- and depression-like behaviours in TGRs and warrant further investigation as a new therapy for certain psychiatric disorders.

scholarly journals Screening of Anxiolytic and Antidepressant of Methanolic Leaves Extract of Syzygium Cumini in Mice

2020 ◽  
Vol 8 (2) ◽  
pp. 91-97
Author(s):  
Ahad Abdul Rehman ◽  
Azra Riaz ◽  
Muhammad Arif Asghar ◽  
Bushra Sikandar ◽  
Moona Baig
Keyword(s):  
Open Field ◽  
Field Test ◽  
Open Field Test ◽  
Tail Suspension Test ◽  
Anxiety And Depression ◽  
High Dose ◽  
Syzygium Cumini ◽  
Immobility Duration ◽  
Plus Maze ◽  
Swimming Test

Background: Anxiety and depression are very common in clinical practice and reduce the overall quality of life. In recent years, various researchers have focused on natural products which are derived from medicinal plants. Studies suggested that diet rich in flavonoids, vitamins and antioxidants are the important components in reduction of anxiety and depression. Objective: Hence current investigation was aimed to assess the anxiolytic and antidepressant effects of Syzygium cumini in mice at 125, 250 and 500 mg/kg. Methods: These effects were mainly evaluated twice at 8th and 15th days by elevated plus maze, open field test, forced swimming test and tail suspension test. Results and Conclusion: In open field test S. cumini showed escalation rearing in numbers and its duration which indicates improved exploratory behavior and locomotor activity of the animals. In EPM, there was increase in entries numbers and time spent in open arm. Decrease in immobility duration observed at low dose while high dose increased immobility duration in FST. Hence outcomes of current study indicate that S. cumini have anxiolytic and anti-depressant effect.

Anxiogenic and anxiolytic effects of memantine injected into the ventral hippocampus in male stressed mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Sahraei ◽  
Hedayat Sahraei ◽  
Masoomeh Rahimi ◽  
Maryam Khosravi ◽  
Mahin Ganjkhani ◽  
...  
Keyword(s):  
Forced Swimming Test ◽  
Elevated Plus Maze ◽  
Ventral Hippocampus ◽  
Middle Part ◽  
Anxiety And Depression ◽  
Stress Effect ◽  
Plus Maze ◽  
Nmda Glutamate Receptors ◽  
Swimming Test ◽  
Shock Stress

Abstract Objectives The effects of intra-ventral hippocampal memantine administration in male NMRI stressed mice were studied. Methods Two stainless steel gauge 23 guide cannulas were placed in the middle part of the mice ventral hippocampus using stereotaxic coordination. Seven days later, the animals were undergone to the stress protocol as follows: They experience four consecutive electro-foot shock stress sessions lasting for 10 min. Five or 30 min before each stress session, the animals received intra-ventral hippocampal (0.1, 1 and, 5 µg/mouse) or intraperitoneal (1, 5, and 10 mg/kg) memantine respectively. Eight days after stress termination, the animals were tested either for the maintenance of either anxiety (elevated plus maze) or depression (forced swimming test). Results Animals show anxiety eight days after stress termination. Intra-ventral hippocampal infusion of memantine (5 µg/mouse) 5 min before stress inhibited the anxiety-like behaviors. However, other doses of the drug exacerbate the stress effect. The drug, when injected peripherally exacerbated the stress effect in all doses. The drug by itself had no effect. In addition, animals also show depression nine days after stress termination and memantine (0.1, 1, and 5 µg/mouse) reduced the stress effect. The drug (0.1 µg/mouse) by itself induced depression in the animals. However, the drug when injected peripherally reduced the stress effect in all doses. Conclusions It could be concluded that NMDA glutamate receptors in the ventral hippocampus may play a pivotal role in the mediation of maintenance of anxiety and depression induced by stress in the mice.

scholarly journals Protective Effects of Two Halophilic Crude Extracts from Pseudomonas zhaodongensis and Bacillus stratosphericus against Memory Deficits and Anxiety- and Depression-Like Behaviors in Methionine-Induced Schizophrenia in Mice Focusing on Oxidative Stress Status

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yousra Massaoudi ◽  
Jaouad Anissi ◽  
Radu Lefter ◽  
Andrei Lobiuc ◽  
Khalid Sendide ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Negative Symptoms ◽  
Forced Swimming Test ◽  
Anxiety And Depression ◽  
Protective Effects ◽  
Crude Extracts ◽  
Y Maze ◽  
Plus Maze ◽  
Oxidative Stress Status ◽  
Swimming Test

Recently, the implication of oxidative stress in behavioral-like disorders has received a lot of attention. Many studies were interested in searching for new natural compounds with protective effects on behavioral-like disorders by focusing on oxidative stress as the main causal factor. Here, we assess the potential effect of cell-free extracts from halophilic bacteria on memory, anxiety, and depression-related behaviors in mice, as well as on cognitive deficits, negative symptoms, and some oxidative stress biomarkers in methionine-induced mice models of schizophrenia. Firstly, crude extracts of bacteria isolated from the Dead Sea were screened for their effects on memory and anxiety- and depression-like behaviors through Y-maze, elevated plus maze, and forced swimming test, respectively, using two doses 60 mg/kg and 120 mg/kg. Then, 120 mg/kg of two bacterial crude extracts, from two strains designated SL22 and BM20 and identified as Bacillus stratosphericus and Pseudomonas zhaodongensis, respectively, with significant contents of phenolic and flavonoid-like compounds, were selected for the assessment of cognitive and negative symptom improvement, as well as for their effects on oxidative stress status in methionine-induced mice models of schizophrenia using six groups (controls, methionine, crude extracts solely, and combinations of crude extracts and methionine). Results showed that the administration of the crude extracts caused a significant increase in the spontaneous alternations in the Y-maze task, the time spent in open arms of the elevated plus maze, and a decrease in immobility time in the forced swimming test in comparison with the control group. Furthermore, the administration of bacterial extracts seemed to diminish disorders related to cognitive and negative symptoms of schizophrenia and to improve the oxidative state in the temporal lobes, in comparison with the methionine group. Our findings suggest substantial antioxidant and anti-neuropsychiatric effects of the crude extracts prepared from Pseudomonas zhaodongensis strain BM20 and Bacillus stratosphericus strain SL22 and that further studies are needed to purify and to determine the active fraction from the extracts.

scholarly journals Anxiety And Depressive Effects Of Antiepileptics In Animal Models

2021 ◽  
Author(s):  
Yasemin Karal ◽  
Mehmet Azizoğlu ◽  
Çetin Hakan Karadağ ◽  
Serap Tevhide Karasalihoğlu
Keyword(s):  
Cognitive Impairment ◽  
Animal Models ◽  
Forced Swimming Test ◽  
Elevated Plus Maze ◽  
Anxiety And Depression ◽  
Plus Maze ◽  
Epileptic Patients ◽  
Term Administration ◽  
Swimming Test

Aim: Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants Levetiracetam (60 mg/kg, p.o.), Vigabatrin (100 mg/kg, p.o.) and Sodyum Valproat (50 mg/kg, p.o.) on anxiety and depression on animal models of rats. Materials and methods: Elevated plus maze (EPM) and Forced swimming test- Porsolt tests (FST) were carried out after 12th weeks of the lifes of rats those that took the three anticonvülsion therapy administration. Results: The results of the present study indicate that none of the three antikonvülsan drugs taken in childhood period impairs anxiety and depression in adult hood. Conclusion: To conclude, long term administration of Levetiracetam, Vigabatrin and Sodyum Valproat have no effect on the anxiety and depression at adulthood time if epilepsy does not exist.

Mirtazapine attenuates anxiety- and depression-like behaviors in rats during cocaine withdrawal

2019 ◽  
Vol 33 (5) ◽  
pp. 589-605 ◽  
Author(s):  
Susana Barbosa Méndez ◽  
Alberto Salazar-Juárez
Keyword(s):  
Field Tests ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Cocaine Withdrawal ◽  
Chronic Cocaine ◽  
Plus Maze ◽  
Swimming Test ◽  
Drug Dependent ◽  
Sites Of Action ◽  
Different Doses

Background: Anxiety and depression, key symptoms of the cocaine withdrawal syndrome in human addicts, are considered the main factors that precipitate relapse in chronic cocaine addiction. Preclinical studies have found that rodents exposed to different withdrawal periods show an increase in anxiety and depressive-like behavior. Mirtazapine – a tetracyclic medication – is used primarily to treat depression and, sometimes, anxiety. It has also successfully improved withdrawal symptoms in drug-dependent patients. Aim: This study sought to determine whether chronic dosing of mirtazapine during cocaine withdrawal reduced depression- and anxiety-like behaviors that characterize cocaine withdrawal in animals. Methods: Cocaine pre-treated Wistar rats were subjected to a 60-day cocaine withdrawal period during which depression- and anxiety-like behaviors were evaluated in open field tests (OFT), the elevated plus-maze (EPM), the light–dark box test (LDT), the forced swimming test (FST) and spontaneous locomotor activity (SLA). Results: We found that chronic dosing with different doses of mirtazapine (30 and 60 mg/kg) decreased depression- and anxiety-like behaviors induced by different doses of cocaine (10, 20 and 40 mg/kg) during the 60-day cocaine withdrawal. Interpretation: Our results suggest that the pharmacological effect of mirtazapine on its target sites of action (α2-adrenergic and 5-HT2A and 5-HT3 receptors) within the brain may improve depression- and anxiety-like behaviors for long periods. Conclusion: Therefore, the findings support the use of mirtazapine as a potentially effective therapy to reduce anxiety and depressive-like behavior during cocaine withdrawal.

Cinnamamides from Piper capense with affinity to the benzodiazepine site on the GABAA receptor

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
ME Pedersen ◽  
HB Rasmussen ◽  
B Metzler ◽  
GI Stafford ◽  
J van Staden ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Benzodiazepine Site

scholarly journals Involvement of 5-HT1AReceptors in the Anxiolytic-Like Effects of Quercitrin and Evidence of the Involvement of the Monoaminergic System

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jian Li ◽  
Qian-tong Liu ◽  
Yi Chen ◽  
Jie Liu ◽  
Jin-li Shi ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Elevated Plus Maze ◽  
Experimental Models ◽  
Control Group ◽  
Repeated Treatment ◽  
Plus Maze ◽  
Way 100635 ◽  
Marble Burying ◽  
Monoaminergic System ◽  
Light Dark Box

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.

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