THE SULPIRIDE CORRECTION OF BEHAVIORAL DISORDERS IN ALCOHOLIZED WHITE MALE RATS WITH DIFFERENT DEGREES OF DEPRESSION

2019 ◽  
pp. 19-28
Author(s):  
Г.А. Фролова
Keyword(s):  
Open Field ◽  
Behavioral Disorders ◽  
Open Space ◽  
Elevated Plus Maze ◽  
Total Duration ◽  
Exploratory Activity ◽  
Male Rats ◽  
Behavioral Activity ◽  
Porsolt Test ◽  
Plus Maze

Целью исследования является оценка коррекции поведенческих нарушений, вызванных двухнедельной алкоголизацией у самцов белых крыс, путем блокирования сульпиридом ауторецепторов дофамина с учетом индивидуально-типологических особенностей животных. Методика. Эксперимент был выполнен на 40 половозрелых крысах-самцах массой 180-220 г. Уровень тревожности крыс определяли в приподнятом крестообразном лабиринте по общему времени пребывания животного на открытом пространстве лабиринта за 5 мин тестирования и числу повторных выходов на него. Двигательную и исследовательскую активность, а также число актов груминга животных оценивали в тесте открытого поля в течение 5 мин. Уровень депрессивности животных устанавливали с помощью теста Порсолта с подсчетом количества и общей продолжительности периодов полной иммобильности (неподвижности) животного. По количеству фекальных болюсов судили об эмоциональности животных. После исходного (контрольного) тестирования в батарее вышеуказанных тестов животные были разделены на три подгруппы согласно выраженности депрессивности в тесте Порсолта. Алкоголизацию проводили в течение 14 сут путем внутрибрюшинного введения раствора этанола в виде 10% раствора из расчета 2 г/кг веса животного, после чего животные проходили повторное тестирование в поведенческих тестах. Сульпирид («Eglonyl», Sanofi Winthrop Industrie, France) вводили в течение 14 сут в дозе 10 мг/кг, внутрибрюшинно, после чего животные снова проходили тестирование. Результаты. Двухнедельная алкоголизация приводит к увеличению тревожности и депрессивности самцов с исходно низким и средним уровнем депрессивности, на что указывает сокращение пребывания животных данных подгрупп на открытом пространстве приподнятого крестообразного лабиринта (p<0,01), уменьшение числа повторных выходов на него (p<0,05) и значительное увеличение общего времени неподвижности в тесте Порсолта (p<0,01). Последующее введение сульпирида корректирует анксиогенный и депрессогенный эффекты алкоголизации у самцов этих подгрупп. Исходно высокодепрессивные животные не проявили чувствительности к 14-дневному введению этанола и последующему блокированию D2/D3-рецепторов дофамина в приподнятом крестообразном лабиринте и тесте Порсолта. Введение этанола в течение 14 дней угнетает исследовательскую активность (p<0,01) самцов в открытом поле независимо от исходного уровня их депрессивности и двигательную (p<0,01) у низкодепрессивных животных. Последующее введение сульпирида не привело к компенсации эффекта алкоголизации на показатели поведенческой активности в открытом поле. У низкодепрессивных самцов на фоне двухнедельной алкоголизации развивается депрессивноподобное состояние, характеризующееся выраженным поведенческим дефицитом в открытом поле. Двухнедельная алкоголизация приводит к значительному (в 2-3,5 раз, p<0,01) росту эмоциональности независимо от исходного уровня депрессивности крыс, что полностью корректируется последующим введением сульпирида у высокодепрессивных самцов, и к частичному снижению проявлений эмоциональности у низко- и среднедепрессивных животных. Заключение. Полученные результаты свидетельствуют о возможности коррекции тревожных и депрессивных нарушений, возникших на фоне двухнедельной алкоголизации, сульпиридом с учетом индивидуально-типологических особенностей организма. The aim of the study was to evaluate correction of behavioral disorders with sulpiride, a dopamine autoreceptor inhibitor, in alcoholized rats taking into account individual typological features of the animals. Methods. Experiments were performed on sexually mature male rats weighing 180-220 g. The level of anxiety was determined in the elevated plus-maze by the total time of stay in and number of exits from the open space of the maze during 5 minutes of testing. Locomotor and exploratory activity and grooming behavior were assessed in the open field for 5 minutes. The severity of animal depression was determined using the standard Porsolt test by the number and total duration of immobility periods. The emotional state of animals was evaluated by the number of fecal boluses. After the initial (control) tests, the rats were divided into three subgroups based on the severity of depression as determined in the Porsolt test. Alcoholism was modeled by intraperitoneal injections of 10% ethanol (2 g/kg body weight) for 14 days. Then the animal behavior was re-tested. Sulpiride (Eglonyl, Sanofi Winthrop Industrie, France) was administered for 14 days at a dose of 10 mg/kg, intraperitoneally; then the animals were tested again. Results. Two-week alcoholization resulted in increased anxiety and depression of rats with low and medium depression degree at baseline. These disorders were evident from shortened stay of these animals in the open space of elevated plus-maze, reduced number of repeated exits from the open space, and a significant increase in the total time of immobility in the Porsolt test. The subsequent sulpiride treatment corrected the anxiogenic and depressogenic effects of alcoholism in male rats of these subgroups. Originally high-depressive animals did not show a sensitivity to the 14 day-administration of ethanol and subsequent inhibition of D2/D3-dopamine receptors in the elevated plus-maze and Porsolt test. Administration of ethanol for 14 days suppressed both the exploratory activity of rats in the open field regardless of their baseline degree of depression, and the locomotor activity of low-depressive animals. The subsequent sulpiride treatment did not abolish the effect of alcohol on the behavioral activity in the open field. Low-depressive alcoholized males developed a depression-like condition characterized by a marked behavioral deficit in the open field. The two-week alcoholization resulted in a significant (2-3.5 times) increase in the emotionality irrespective of the baseline degree of depression. This disorder was fully corrected by the sulpiride treatment in high-depressive rats and partially reduced the signs of emotionality in low- and medium-depressive animals. Conclusion. The study showed a possibility for correction of anxiety and depressive disorders induced by two weeks of modeled alcohol abuse with sulpiride depending on individual typological features of animals.

Effect of Surfagon on Open Field and Elevated Plus Maze Behavior of Gonadectomized and Non-Gonadectomized Male Rats

2019 ◽  
Vol 168 (1) ◽  
pp. 52-54
Author(s):  
O. O. Masalova ◽  
S. B. Kazakova ◽  
T. N. Savateeva-Lyubimova ◽  
K. V. Sivak ◽  
N. S. Sapronov ◽  
...  
Keyword(s):  
Open Field ◽  
Elevated Plus Maze ◽  
Male Rats ◽  
Plus Maze

scholarly journals Effect of Short Time Exposure of Local ELF-MFs on Sleepiness Induced in Male Rats

2021 ◽  
Vol 0 (0) ◽  
pp. 1-22
Author(s):  
Elnaz Azizi ◽  
◽  
Fatemeh Ayoobi ◽  
Ali Shamsizadeh ◽  
Amir Moghadam-Ahmadi ◽  
...  
Keyword(s):  
Serum Level ◽  
Open Field ◽  
Field Test ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Male Rats ◽  
Time Exposure ◽  
Plus Maze ◽  
Before And After ◽  
Short Time

Introduction: Lack of high-quality sleep causes serious side effects like anxiety and changes in plasma concentration of oxalate. The current study aimed to investigate the impact of local extremely low frequency magnetic fields (ELF-MFs) on inducing sleep (sleepiness) and anxiety in male rats. Methods: In this experimental study, 40 male rats were allocated in four groups (n=10). The ELF-MFs exposure (0, 10 and 18 Hz) was applied with intensity 200µT for three days (10 min/day). Sham-treated animal did not receive ELF-MF. Serum level of oxalic acid (OA) and sleepiness were measured both before first and after last exposure to ELF-MF or sham. Anxiety, sleepiness and OA were measured by using elevated plus maze, open-field test (OFT) and ELISA test, respectively. Results: Comparison of oxalate levels between before and after exposure to ELF-MF revealed that ELF-MF (10 Hz) decreased the serum level of oxalate (p<0.05). Comparison of the percent of open:closed arm entry (in elevated plus maze) between before and after exposure to ELF-MF revealed significant differences. Also, frequency, velocity and distance moved were decreased in the open-field test. Conclusion: Results of the present study demonstrated that ELF-MF with short time exposure may modulate the metabolism of OA and may modulate anxiety-like behavior or kind of induction of sleepiness in male rats.

scholarly journals Dorsal Hippocampus ERK2 Signaling Mediates Anxiolytic-Related Behavior in Male Rats

2019 ◽  
Vol 3 ◽  
pp. 247054701989703
Author(s):  
Jorge A. Sierra-Fonseca ◽  
Lyonna F. Parise ◽  
Francisco J. Flores-Ramirez ◽  
Eden H. Robles ◽  
Israel Garcia-Carachure ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Open Field ◽  
Field Test ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Dorsal Hippocampus ◽  
Male Rats ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Plus Maze

Background Anxiety disorders are the most common neuropathologies worldwide, but the precise neuronal mechanisms that underlie these disorders remain unknown. The hippocampus plays a role in mediating anxiety-related responses, which can be modeled in rodents using behavioral assays, such as the elevated plus maze. Yet, the molecular markers that underlie affect-related behavior on the elevated plus maze are not well understood. Methods We used herpes simplex virus vector delivery to overexpress extracellular signal-regulated kinase-2, a signaling molecule known to be involved in depression and anxiety, within the dorsal hippocampus of adult Sprague-Dawley male rats. Three days post virus delivery, we assessed anxiety-like responses on the elevated plus maze or general locomotor activity on the open field test. Results When compared to controls, rats overexpressing extracellular signal-regulated kinase-2 in the dorsal hippocampus displayed an anxiolytic-like phenotype, per increases in time spent in the open arms, and less time in the closed arms, of the elevated plus maze. Furthermore, no changes in locomotor activity as a function of virus infusion were observed on the open field test between the experimental groups. Conclusion This investigation demonstrates that virus-mediated increases of extracellular signal-regulated kinase-2 signaling, within the hippocampus, plays a critical role in decreasing anxiogenic responses on the rat elevated plus maze. As such, our data provide construct validity, at least in part, to the molecular mechanisms that mediate anxiolytic-like behavior in rodent models for the study of anxiety.

scholarly journals Participation ofGABAAChloride Channels in the Anxiolytic-Like Effects of a Fatty Acid Mixture

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Juan Francisco Rodríguez-Landa ◽  
Rosa Isela García-Ríos ◽  
Jonathan Cueto-Escobedo ◽  
Blandina Bernal-Morales ◽  
Carlos M. Contreras
Keyword(s):  
Open Field ◽  
Field Test ◽  
Chloride Channels ◽  
Wistar Rats ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Acid Mixture ◽  
Plus Maze ◽  
Gaba Binding ◽  
Defensive Burying

Human amniotic fluid and a mixture of eight fatty acids (FAT-M) identified in this maternal fluid (C12:0, lauric acid, 0.9 μg%; C14:0, myristic acid, 6.9 μg%; C16:0, palmitic acid, 35.3 μg%; C16:1, palmitoleic acid, 16.4 μg%; C18:0, stearic acid, 8.5 μg%; C18:1cis, oleic acid, 18.4 μg%; C18:1trans, elaidic acid, 3.5 μg%; C18:2, linoleic acid, 10.1 μg%) produce anxiolytic-like effects that are comparable to diazepam in Wistar rats, suggesting the involvement ofγ-aminobutyric acid-A (GABAA) receptors, a possibility not yet explored. Wistar rats were subjected to the defensive burying test, elevated plus maze, and open field test. In different groups, threeGABAAreceptor antagonists were administered 30 min before FAT-M administration, including the competitive GABA binding antagonist bicuculline (1 mg/kg),GABAAbenzodiazepine antagonist flumazenil (5 mg/kg), and noncompetitiveGABAAchloride channel antagonist picrotoxin (1 mg/kg). The FAT-M exerted anxiolytic-like effects in the defensive burying test and elevated plus maze, without affecting locomotor activity in the open field test. TheGABAAantagonists alone did not produce significant changes in the behavioral tests. Picrotoxin but not bicuculline or flumazenil blocked the anxiolytic-like effect of the FAT-M. Based on the specific blocking action of picrotoxin on the effects of the FAT-M, we conclude that the FAT-M exerted its anxiolytic-like effects throughGABAAreceptor chloride channels.

IMPACT OF EARLY LIFE STRESS ON ANTI-DEPRESSANT SENSITIVITY

2021 ◽  
pp. 123-132
Author(s):  
V.A. Vokina
Keyword(s):  
Open Field ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Anxiety Level ◽  
Male Rats ◽  
Porsolt Test ◽  
The Impact ◽  
Sexually Mature

Long-term consequences of impaired perinatal development are very significant. They appear during the neonatal period and in the first years of life, and persist during ontogenesis. There is little data on the impact of any prenatal factors on the sensitivity of a sexually mature organism to medications. The aim of the study is to assess the impact of early life stress on the development of individual antidepressant sensitivity. Materials and Methods. The authors conducted the experiments on sexually mature outbred male rats. To simulate the early life stress, a standard protocol was used. From the 2nd to 15th days of the postnatal period the pup rats were separated from their mother for 3 hours and kept in an incubator. The open-field test, Porsolt test and Sucrose consumption test were used to determine rat’s anxiety level as well as motor, orientation and exploratory activity at puberty. Then, for 14 days, the rats were intragastrically administered with a fluoxetine solution (10 mg/kg/daily), followed by their full examination. Statistical analysis of results was performed using the Mann-Whitney U-test to compare unrelated groups and Wilcoxon's test to compare related groups. Results. Fluoxetine did not have a pronounced antidepressant effect in animals that survived the early life stress. Such animals demonstrated passive floating during the Porsolt test, without any changes in immobility time. When testing in an open field, a sharp increase in the number of freezing behavior was observed, which was an indicator of an increased anxiety level in animals. Conclusion. The results obtained indicate that the long-term effects of neonatal stress may be associated with a change in antidepressant sensitivity or an increase in development of unwanted adverse reactions. Keywords: early life stress, depression, antidepressants, fluoxetine, rats. Отдаленные последствия нарушения перинатального развития весьма значительны и не только проявляются в период новорожденности и в первые годы жизни, но и сохраняются в период онтогенеза. Данные о влиянии каких-либо пренатальных факторов на чувствительность половозрелого организма к действию лекарственных веществ в доступной литературе представлены незначительно. Цель исследования – оценить роль стресса раннего периода жизни в формировании индивидуальной чувствительности к действию антидепрессантов. Материалы и методы. Эксперименты проведены на половозрелых беспородных крысах-самцах. Для моделирования стресса раннего периода жизни использовали стандартный протокол, подразумевающий отделение детенышей от матери со 2-го по 15-й дни постнатального периода на 3 ч в условиях инкубатора. В половозрелом возрасте проводили оценку уровня тревожности, двигательной и ориентировочно-исследовательской активности крыс в условиях теста открытого поля, теста Порсолта и теста «Потребление раствора сахарозы». Затем в течение 14 дней крысам внутрижелудочно вводили раствор флуоксетина (10 мг/кг/сут), после чего обследование повторяли в том же объеме. Статистический анализ результатов исследования проводили с использованием U-критерия Манна–Уитни для сравнения несвязанных групп и критерия Вилкоксона для сравнения связанных групп. Результаты. У животных, переживших стресс раннего периода жизни, флуоксетин не оказывал выраженного антидепрессантного действия. У данных животных в тесте Порсолта преобладало пассивное плавание, без изменения длительности иммобильности. При тестировании в открытом поле наблюдалось резкое повышение числа актов фризинга, что является показателем повышенного уровня тревожности у животных. Выводы. Полученные результаты свидетельствуют о том, что отдаленные последствия неонатального стресса могут быть связанны с изменением чувствительности к действию антидепрессантов или повышением риска развития нежелательных побочных реакций. Ключевые слова: стресс раннего периода жизни, депрессия, антидепрессанты, флуоксетин, крысы.

Neuropharmacological Activity of Various Fractions Obtained from Solanum aethiopicum (Linn.) Fruit in Mice.

2020 ◽  
Vol 1 (5) ◽  
pp. 12-23
Author(s):  
A.R. Abubakar ◽  
◽  
I.H. Sani ◽  
S. Malami ◽  
A.H. Yaro ◽  
...  
Keyword(s):  
Open Field ◽  
Elevated Plus Maze ◽  
Toxicity Testing ◽  
Aqueous Fraction ◽  
Solanum Aethiopicum ◽  
Elevated Plus Maze Test ◽  
Board Test ◽  
Plus Maze ◽  
Hole Board ◽  
Hole Board Test

Background: Solanum aethiopicum (L.), family Solanaceae, is known as garden eggs. The fruit is used in the treatment of insomnia, diabetes and constipation. Objective: The aim of this study was to evaluate anxiolytic-like activity of fractions obtained from crude methanol extract of Solanum aethiopicum fruit. Method: Acute toxicity testing was conducted according to the OECD guidelines 420 via oral and intraperitoneal routes (ip). n-Hexane (HF), chloroform (CHF), ethyl-acetate (EAF), n-butanol (BF) and residual aqueous fraction (RAF) at doses of 25, 50 and 100 mg/kg ip were experimented using the open field, elevated plus maze, staircase, light dark box and hole-board tests. Results: Results: In open field test, there was statistically significant increase in frequency of central square entry by EAF 25mg/kg, 50mg/kg and 100mg/kg and RAF 25mg/kg, 50mg/kg and 100mg/kg all at p<0.05 compared to distilled water (D/W) group. Elevated plus maze test showed statistically significant increases in open arm entry and duration by CHF 25mg/kg, RAF 25mg/kg and 50mg/kg again at p<0.05. Also, in the staircase test, statistically significant decrease in frequency of rearing with no effect on step climbing was observed by RAF 25mg/kg (p< 0.05) compared to D/W. Light and dark box test produced increased light box entry and duration by EAF 25mg/kg, RAF 25mg/kg and 50mg/ kg at p<0.05. Furthermore, the hole -board test showed statistically significant increases in number of head dips by EAF 50mg/kg and 100mg/kg as well as RAF 25mg/kg, 50mg/kg and 100 mg/kg at p<0.05. Conclusion: The fractions obtained from Solanum aethiopicum fruits possesses anxiolytic-like activity.

scholarly journals Aqueous Extract of Semen Ziziphi Spinosae Exerts Anxiolytic Effects during Nicotine Withdrawal via Improvement of Amygdaloid CRF/CRF1R Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Changhong Gu ◽  
ZhengLin Zhao ◽  
Xiaodong Zhu ◽  
Tong Wu ◽  
Bong Hyo Lee ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Elevated Plus Maze ◽  
Plasma Corticosterone ◽  
Nicotine Withdrawal ◽  
Corticotropin Releasing Factor ◽  
Central Nucleus ◽  
Male Rats ◽  
General Anxiety ◽  
Plus Maze

Anxiety during nicotine withdrawal (NicW) is a key risk factor for smoking relapse. Semen Ziziphi Spinosae (SZS), which is a prototypical hypnotic-sedative herb in Oriental medicine, has been clinically used to treat insomnia and general anxiety disorders for thousands of years. Thus, the present study evaluated the effects of the aqueous extract of SZS (AESZS) on NicW-induced anxiety in male rats that received subcutaneous administrations of nicotine (Nic) (0.4 mg/kg, twice a day) for 7 d followed by 4 d of withdrawal. During NicW, the rats received four intragastric treatments of AESZS (60 mg/kg/d or 180 mg/kg/d). AESZS dose-dependently attenuated NicW-induced anxiety-like behaviors in the elevated plus maze (EPM) tests and 180 mg/kg/d AESZS inhibited NicW-induced increases in plasma corticosterone. Additionally, the protein and mRNA expressions of corticotropin-releasing factor (CRF) and CRF type 1 receptor (CRF1R) increased in the central nucleus of the amygdala (CeA) during NicW, but these changes were suppressed by 180 mg/kg/d AESZS. A post-AESZS infusion of CRF into the CeA abolished the attenuation of anxiety by AESZS and 180 mg/kg/d AESZS suppressed NicW-induced increases in norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the CeA. The present results suggest that AESZS ameliorated NicW-induced anxiety via improvements in CRF/CRF1R and noradrenergic signaling in the CeA.

scholarly journals Staying at the crossroads: assessment of the potential of serum lithium monitoring in predicting an ideal lithium dose

2008 ◽  
Vol 30 (3) ◽  
pp. 215-221 ◽  
Author(s):  
Thiago Zaqueu Lima ◽  
Miriam Marcela Blanco ◽  
Jair Guilherme dos Santos Júnior ◽  
Carolina Tesone Coelho ◽  
Luiz Eugênio Mello
Keyword(s):  
Open Field ◽  
Lithium Chloride ◽  
Elevated Plus Maze ◽  
Lithium Concentration ◽  
Serum Lithium Concentration ◽  
Narrow Therapeutic Range ◽  
Plus Maze ◽  
Sufficient Precision ◽  
Lithium Dose ◽  
Plasmatic Concentration

OBJECTIVE: Lithium has been successfully employed to treat bipolar disorder for decades, and recently, was shown to attenuate the symptoms of other pathologies such as Alzheimer's disease, Down's syndrome, ischemic processes, and glutamate-mediated excitotoxicity. However, lithium's narrow therapeutic range limits its broader use. Therefore, the development of methods to better predict its dose becomes essential to an ideal therapy. METHOD: the performance of adult Wistar rats was evaluated at the open field and elevated plus maze after a six weeks treatment with chow supplemented with 0.255%, or 0.383% of lithium chloride, or normal feed. Thereafter, blood samples were collected to measure the serum lithium concentration. RESULTS: Animals fed with 0.255% lithium chloride supplemented chow presented a higher rearing frequency at the open field, and higher frequency of arms entrance at the elevated plus maze than animals fed with a 50% higher lithium dose presented. Nevertheless, both groups presented similar lithium plasmatic concentration. DISCUSSION: different behaviors induced by both lithium doses suggest that these animals had different lithium distribution in their brains that was not detected by lithium serum measurement. CONCLUSION: serum lithium concentration measurements do not seem to provide sufficient precision to support its use as predictive of behaviors.

scholarly journals Dose-Dependent, Antidepressant, and Anxiolytic Effects of a Traditional Medicinal Plant for the Management of Behavioral Dysfunctions in Animal Models

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989126 ◽  
Author(s):  
Hafiz Muhammad Asif ◽  
Abdul Hayee ◽  
Muhammad Rahil Aslam ◽  
Khalil Ahmad ◽  
Abdul Sattar Hashmi
Keyword(s):  
Open Field ◽  
Elevated Plus Maze ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Tail Suspension ◽  
Hydroalcoholic Extract ◽  
Elevated Plus Maze Test ◽  
Plus Maze ◽  
Immobility Time ◽  
Dose Dependent

The present work was carried out to assess the Onosma bracteatum anxiolytic and antidepressant properties. Swiss albino mice (male) were fed orally with hydroalcoholic extract at different doses 50, 100, and 200 mg 1 hour prior to test with the standard diazepam and fluoxetine. Anxiolytic and antidepressant activities were evaluated by using open field, elevated plus maze, force swimming, and tail suspension test. Results of open field test showed an increase in number of line crossing as well as number of rearing in dosage-dependent design. Although results of elevated plus maze test evidently showed antianxiety effect of O bracteatum by increasing the time spent in open arms along with decreasing the time spent in closed arms in dosage-dependent way. For the evaluation of antidepressant effect, O bracteatum diminished the immobility time and expanded mobility time in forced swim model in dosage-dependent way. Likewise, O bracteatum expanded time span of mobility along with diminished immobility time in tail suspension method in dosage-dependent way. Outcome demonstrated that plant at the dose of 200 mg/kg body weight showed significant potential which was similar to that standard diazepam and fluoxetine. Hence, O bracteatum may be used as potent natural psychotherapeutic agent against the mental disorders.

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