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

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.

2015 ◽  
Vol 73 (2) ◽  
pp. 132-139 ◽  
Author(s):  
Hamid Azizi-Malekabadi ◽  
Masoume Pourganji ◽  
Hoda Zabihi ◽  
Mohsen Saeedjalali ◽  
Mahmoud Hosseini

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.


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 ◽  
...  

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.


2020 ◽  
Vol 8 (2) ◽  
pp. 91-97
Author(s):  
Ahad Abdul Rehman ◽  
Azra Riaz ◽  
Muhammad Arif Asghar ◽  
Bushra Sikandar ◽  
Moona Baig

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.


Author(s):  
Mohammad Sahraei ◽  
Hedayat Sahraei ◽  
Masoomeh Rahimi ◽  
Maryam Khosravi ◽  
Mahin Ganjkhani ◽  
...  

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yousra Massaoudi ◽  
Jaouad Anissi ◽  
Radu Lefter ◽  
Andrei Lobiuc ◽  
Khalid Sendide ◽  
...  

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.


Author(s):  
Jose Carlos Tavares Carvalho ◽  
Aline Ferreira Vaz ◽  
Raiza Marques Vieira Campos ◽  
Kélem Costa Dos Santos ◽  
Benedito Junior Medeiros ◽  
...  

Background: The homeopathic complex Homeo-Pax® has been used as an antidepressant and anxiolytic homeopathic medicine available in Brazil. It is a complex mixture prepared with Aconitum nap. 6cH, Aurum met. 6cH, Phosphorus 6cH, Argentum nitricum 6cH, Arsenicum alb. 6cH, and Valeriana officinalis 3cH. Aims: This study had evaluated the behavior in rats after treatment with Homeo-Pax® in pre-clinical models of depression and anxiety. Mathods: Elevated Plus Maze Test (EPM), Forced Swimming Test (FST), Open Field Test (OFT) and the Rota Rod Test (RRT) behavior assays were used to confirm its activity. In the EPM, the animals treated with Homeo-pax® on the 1st day and until the 20th day of treatment remained longer in the open arms of the maze than on 30th day. This result was statistically significant compared with the control group (p < 0.05). In the FST, the treatment with Homeo-pax® (0.5 ml, p.o) increased the swimming time, compared to the control group. This effect was dependent on treatment time, resulting in a similar effect to that presented by amfepramone (10 mg/kg, p.o). In the OFT, crossing by the animals was significantly increased by the treatment with amfepramone (10mg/kg, p.o), and also with the 30-day treatment with Homeo-pax®. In the RRT, the 30-day treatment with Homeo-pax® (0.5 ml, p.o) did not affect the animals’ motor coordination, compared with the control group, which presented the same behavior. Conclusion: Based on the results obtained, it can be suggested that the homeopathic complex Homeo-pax® has anxiolytic and antidepressant properties without affecting motor coordination capacity.


Author(s):  
Mehmet Hanifi Tanyeri ◽  
Mehmet Emin Buyukokuroglu ◽  
Pelin Tanyeri ◽  
Rumeysa Keles Kaya ◽  
Aykut Ozturk ◽  
...  

Aims: Benign prostatic hyperplasia (BPH) is common urological disease, is characterized by lower urinary tract syndrome, usually associated with sexual dysfunctions. The aim of present study is to investigate the effects of terazosin, silodosin and alfuzosin which are the main treatment options for BPH on depression and anxiety to understand whether these drugs may be effective in BPH caused mood disorders. Study Design: All the drugs were given intraperitoneally (i.p.) in a volume of 0.1 ml per 10 g body weight of mice. Drugs were given 30 min before the experiment. We investigated the effects of terazosin, silodosin and alfuzosin on depression and anxiety, in mice. Place and Duration of Study: Sample: Department of Pharmacology and Department of Urology, Sakarya University, Animal Research Center, between June 2019 and September 2020. Methodology: Here, we examined the effects of terazosin (0.5, 1, 2 mg/kg), silodosin silodosin (1, 3, 10 mg/kg) and alfuzosin (3, 6 and 9 mg/kg) on depression and anxiety by using forced swimming test and elevated plus maze test, respectively, in mice (n:96). Additionally, the locomotor activity was evaluated by open field test. Results: All doses of terazosin, alfuzosin and silodosin significantly increased immobility time, compared to saline group. Silodosin and alfuzosin prolonged the time spent in open arms but terazosin decreased the time spent in open arms compared to saline group. Terazosin, silodosin (1 and 3 mg/kg) and alfuzosin (3 and 6 mg/kg) did not have any effect on the number of entries into the open arms while silodosin (10 mg/kg) and alfuzosin (9 mg/kg) increased the number of entries into open arms. Conclusion: We found that silodosin and alfuzosin had antidepressant and anxiolytic-like effects, while terazosin had depressant and anxiogenic effects. Patients with BPH who need antidepressant and anxiolytic treatment can be treated with a single drug instead of multiple medications.


Author(s):  
Lorena de Souza Almeida ◽  
Ianca Gontijo Cavalcante Santana ◽  
Lorrane Kelle da Silva Moreira ◽  
Larissa Córdova Turones ◽  
Germán Sanz ◽  
...  

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.


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