Diazepam normalizes anxiety in rats with experimental anxiety-depressive state induced by diprotin A in the first postnatal week

Author(s):  
Н.А. Крупина ◽  
Н.Н. Хлебникова

В предыдущих исследованиях мы показали, что у крысят, подвергнутых на второй-третьей неделях постнатального развития действию ингибиторов дипептидилпептидазы IV (ДП-IV), в дальнейшем развивалось смешанное тревожно-депрессивное состояние, которое характеризовалось повышением уровня кортикостерона в сыворотке крови. Трициклический антидепрессант имипрамин купировал проявления депрессивноподобного поведения у таких крыс в тесте принудительного плавания. Данные свидетельствовали в пользу соответствия данных моделей основным критериям валидности - «внешней схожести», прогностическому и конструкционному критериям. Недавно в наших исследованиях была разработана новая модель смешанного тревожно-депрессивного состояния, индуцируемая действием ингибитора ДП-IV дипротина А в первую неделю постнатального развития крысят. Цель настоящего исследования - валидизация данной модели тревожно-депрессивного состояния. Методы. Крысятам опытной группы вводили дипротин А (2 мг/кг, внутрибрюшинно), животным контрольной группы - физиологический раствор. У крыс подросткового возраста и взрослых животных оценивали двигательную активность (тест «Автоматизированное открытое поле»), уровень тревожности (тест «Приподнятый крестообразный лабиринт») и депрессивно-подобное поведение (тест принудительного плавания). Двухмесячным животным однократно вводили анксиолитик диазепам (1,25 мг/кг) с последующей оценкой уровня тревожности. Уровень кортикостерона в сыворотке крови определяли методом твердофазного иммуноферментного анализа. Результаты. Действие дипротина А индуцировало развитие депрессивноподобного поведения у крыс в возрасте 1 и 2 мес., и повышало уровень тревожности у двухмесячных крыс. Содержание кортикостерона в крови таких животных превышало контрольный уровень. Диазепам нормализовал уровень тревожности и привыкание в тесте «Приподнятый крестообразный лабиринт». Заключение. Полученные данные свидетельствуют в пользу валидности новой модели смешанного тревожно-депрессивного состояния у крыс, создаваемой действием ингибитора ДП-IV дипротина А в первую неделю постнатального развития. Earlier we have shown that rat pups treated with dipeptidyl peptidase IV (DP-IV) inhibitors in the second to third postnatal weeks further developed a mixed anxiety-depressive state, which was characterized by increased blood corticosterone. Imipramine, a tricyclic antidepressant, suppressed the depressive-like behavior in such rats in the forced swim test. This supported the consistency of these models with the main criteria of validity, «outward similarity» and predictive and construction criteria. Recently we have developed a new model of mixed anxiety-depressive state, induced by a DP-IV inhibitor, diprotin A, administered in the first postnatal week. The aim of this study was to validate this model of anxiety-depressive state. Methods. Diprotin A (2 mg/kg, i.p.) was administered to rats of the experimental group, and saline - to the control animals. Motor activity (automated open field test), anxiety (elevated plus-maze test), and depressive-like behavior (forced swim test) were evaluated in adolescent and adult rats. Two-month-old animals were injected with a single dose of the anxiolytic diazepam (1.25 mg/kg) followed by the anxiety tests. Serum corticosterone level was measured using enzyme immunoassay. Results. Diprotin A induced depressive-like behavior in rats aged one and two months and increased anxiety in two-month-old rats. In these animals, serum corticosterone concentration exceeded the control level. Diazepam normalized anxiety and habituation in the elevated plus-maze test. Conclusion. The study supported the validity of the new model of mixed anxiety-depressive state in rats induced by the DP-IV inhibitor, diprotin A, administered in the first postnatal week.

2008 ◽  
Vol 60 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Natasa Spasojevic ◽  
Ljubica Gavrilovic ◽  
Sladjana Dronjak

Serotonin and noradrenaline are involved in the mechanisms of action of most antidepressant drugs. We examined the effects of chronic treatment with maprotiline, a selective inhibitor of noradrenaline reuptake, and fluxilan, a selective inhibitor of serotonin reuptake, on the behavior of unstressed controls and chronic unpredictable mild stress (CUMS) model rats in the forced swim test (FST) and elevated plus maze test. Both selective reuptake inhibitors resulted in a significant reduction of time spent in immobility. Climbing was significantly increased in maprotiline- and swimming was exclusively elicited in the fluxilan-treated unstressed control and CUMS rats. Maprotiline-treated ani?mals displayed decreased anxiety and fluxilan-treated rats enhanced anxiety. The obtained results suggest that central noradrenergic and serotonergic systems might be affected differently during FST. The results also demonstrate that the anxiogenic effects of chronic fluxilan treatment are similar to those reported by many other studies. These differences observed for the effects of fluxilan in relation to those reported for maprotiline and probably due to the different phar?macological profiles of these drugs.


2019 ◽  
Vol 23 (1) ◽  
pp. 55-61
Author(s):  
E. Y. Bazhenova ◽  
D. V. Fursenko ◽  
N. V. Khotskin ◽  
I. E. Sorokin ◽  
A. V. Kulikov

Decrease in natural illumination in fall/winter months causes depressive-like seasonal affective disorders in vulnerable individuals. Obesity is another risk factor of depression. The lethal yellow (AY) mutation causes ectopic expression of agouti protein in the brain. Mice heterozygous for AY mutation (AY/a) are obese compared to their wild-type littermates (a/a). The main aims of the study were to investigate the effects of AY mutation, photoperiod and the interaction between these factors on daily activity dynamics, feeding, locomotor and exploratory activities, anxiety-related and depressive-like behaviors in mild stress condition. Six weeks old mouse males of AY/a and a/a lines were divided into four groups eight animals each and exposed to long- (14 h light and 10 h darkness) or short- (4 h light and 20 h darkness) day conditions for 28 days. Then the behavior of these mice was successively investigated in the home cage, open field, elevated plus-maze and forced swim tests. We did not observed any effect of AY mutation on the general activity, water and food consumption in the home cage; locomotion and exploration in the open field test; anxiety-related behavior in the open field and elevated plus-maze tests. At the same time, AY mutation increased depressive-like immobility time in the forced swim test (F1.28 = 20.03, p = 0.00012). Shortday conditions decreased nocturnal activity in the home cage, as well as locomotion (F1.28 = 16.33, p = 0.0004) and exploration (F1.28 = 16.24, p < 0.0004) in the open field test. Moreover, short-day exposition decreased time spent in the center of the open field (F1.28 = 6.57, p = 0.016) and in the open arms of the elevated plus-maze (F1.28 = 12.08, p = 0.0017) tests and increased immobility time in the forced swim test (F1.28 = 9.95, p = 0.0038). However, no effect of the interaction between AY mutation and photoperiod on immobility time in the forced swim test was observed. Therefore, short-day photoperiod and AY mutation increased depressive-like behavior in the forced swim test by means of different mechanisms.


2011 ◽  
Vol 86 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Celio Estanislau ◽  
Anna Carolina Ramos ◽  
Paula Daniele Ferraresi ◽  
Naiara Fernanda Costa ◽  
Heloisa Maria Cotta Pires de Carvalho ◽  
...  

Author(s):  
Meera Sumanth ◽  
Prajwala R. Khapale

Background: Many studies have indicated that inflammation and depression are associated with each other. Present study was taken up to prove antidepressant effect of aspirin and diclofenac sodium.Methods: The present study was divided into 6 phases with 5 groups of animals N=10. In study 1, C57Bl mice were used and in remaining 4 studies swiss albino mice. Amitriptyline was standard drug used. For each study first group of animals was treated with a saline solution 1ml P.O., and second group of animals injected with 0.1 ml of 2% formalin. In group 3, 4, 5 animals depression was produced by stressors and treated with aspirin 14mg/kg P.O., diclofenac sod. 10 mg/kg P.O. and amitriptyline 10 mg/kg P.O., respectively. Antidepressant activity of aspirin and diclofenac sodium was determined by using forced swim test, tail suspension test, elevated plus maze test and light dark box test. Inflammatory mediators (IL-6, TNF-α) and central neurotransmitters (5-HT, NE, Ach) were estimated.Results: In light dark box test, latency of first crossing, time spent in dark area were decreased and no. of crossing increased significantly in the aspirin, diclofenac sod. treated animals. In forced swim test, the immobility time was decreased. Swiss albino mice treated with aspirin, diclofenac sod. showed decreased concentration of IL-6 and TNF-α and increased concentration of serotonin, nor epinephrine and acetylcholine. In elevated plus maze test, no. of open arm, closed arm entries, time spent in open arm increased and time spent in closed arm decreased. In tail suspension test immobility time was decreased.Conclusions: Aspirin and diclofenac sodium has antidepressant activity.


2010 ◽  
Vol 3 (2) ◽  
pp. 245-249 ◽  
Author(s):  
Flavia Gomes ◽  
Marília Greidinger ◽  
Marcelo Salviano ◽  
Kalliu Carvalho Couto ◽  
Graziela Ferreira Scaperlli ◽  
...  

2020 ◽  
Vol 75 (11-12) ◽  
pp. 409-415
Author(s):  
Hiroshi Ueno ◽  
Atsumi Shimada ◽  
Shunsuke Suemitsu ◽  
Shinji Murakami ◽  
Naoya Kitamura ◽  
...  

AbstractHexanal is a 6-carbon aldehyde that smells like green leaves and urine to mammals. However, its physiological effects remain unclear. In particular, the effects of hexanal inhalation on the central nervous system have not been clarified. We investigated hexanal inhalation in mice and conducted a series of behavioral experiments to examine the neuropsychological effects of hexanal. After inhaling hexanal emissions for 30 min, mice were subjected to an open field test, a hot plate test, a grip strength test, an elevated plus maze test, a Y-maze test, a tail suspension test, and a forced swim test to examine the effects of hexanal odor on mouse behavior. Compared to controls, mice that inhaled hexanal exhibited reduced anxiety-like behavior in the elevated plus maze test. In addition, mice that inhaled hexanal displayed significantly improved spatial cognitive ability in the Y-maze test. However, in some behavioral experiments there was no significant difference between control mice and mice that inhaled hexanal. The results of this study suggest that hexanal inhalation causes anxiolytic effects and improves cognitive function in mice. These findings may have implications for safety management procedures and determining the effective use of household goods containing hexanal, though further work is required.


2020 ◽  
Vol 34 (8) ◽  
pp. 901-913
Author(s):  
Willian Lazarini-Lopes ◽  
Fabiana Corsi-Zuelli ◽  
Cláudia M Padovan

Background: Exposure to stressful aversive situations induces physiological and behavioral changes. Serotonin has been suggested to mediate such changes, as well as adaptation to stressful events. Serotoninergic projections arising from the median raphe nucleus to the dorsal hippocampus have been suggested to promote adaptation to chronic aversive stimuli. Such pathway may involve serotonin type 1a receptor-mediated neurotransmission. However, the serotonin 7 receptor can also be found in the median raphe nucleus and may be involved in mechanisms underlying response to stress. Aims: In this work we sought to investigate if activation of serotonin type 7 receptors would attenuate stress-induced deficits in different animal models of depression. Methods: Male Wistar rats with a guide-cannula aimed to the median raphe nucleus were submitted to restraint or forced swim stress and were tested in an elevated plus maze or forced swim test, respectively, 24 h later. SB 258741 (serotonin type 7 receptor antagonist) and/or LP 44 (serotonin type 7 receptor agonist) were administered intra-median raphe nucleus immediately before or after exposure to stress or before test. Control groups received intra-median raphe nucleus treatment 24 h or immediately before test in the elevated plus maze or forced swim test. Results: LP 44 attenuated restraint-induced exploratory deficits independently of the moment it was administered. Similar results were observed in the forced swim test, with the exception on post-stress condition. These effects on adaptation to stress induced by serotonin type 7 receptor activation were prevented by previous treatment with SB 258741. Conclusions: Our data support the idea that activation of median raphe nucleus serotonin 7 receptor is important to the development of adaptation to stress.


2012 ◽  
Vol 117 (3) ◽  
pp. 629-637 ◽  
Author(s):  
Ryan C. Turner ◽  
Michael J. Seminerio ◽  
Zachary J. Naser ◽  
J. Neal Ford ◽  
Samantha J. Martin ◽  
...  

Object Despite the role of aging in development of neurological and neurodegenerative diseases, the effects of age are often disregarded in experimental design of preclinical studies. Functional assessment increases the clinical relevance of animal models of neurological disease and adds value beyond traditional histological measures. However, the relationship between age and functional impairment has not been systematically assessed through a battery of functional tests. Methods In this study, various sensorimotor and behavioral tests were used to evaluate effects of aging on functional performance in naive animals. Sensorimotor measures included locomotor activity; Rotarod, inclined plane, and grip-strength testing; and modified Neurological Severity Score. The Morris water maze was used to examine differences in learning and memory, and the elevated plus maze and forced swim test were used to assess anxiety-like and depressive-like behaviors, respectively. Results Older Sprague-Dawley rats (18–20 months) were found to perform significantly worse on the inclined plane tests, and they exhibited alterations in elevated-plus maze and forced swim test compared with young adult rats (3–4 months). Specifically, older rats exhibited reduced exploration of open arms in elevated plus maze and higher immobility time in forced swim test. Spatial acquisition and reference memory were diminished in older rats compared with those in young adult rats. Conclusions This study demonstrates clear differences between naive young adult and older animals, which may have implications in functional assessment for preclinical models of neurological disease.


2020 ◽  
Vol 14 (1) ◽  
pp. 36-51 ◽  
Author(s):  
George L. da Silva Oliveira ◽  
José C. Correia L. da Silva ◽  
Ana P. dos Santos C. L da Silva ◽  
Chistiane M. Feitosa ◽  
Fernanda R. de Castro Almeida

Background: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with β-caryophyllene is still little discussed. Objectives: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of β-caryophyllene (β-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. Methods: This study evaluated the neurobehavioral effects of β-CBP using the open field test, rota-rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. Results:: The results demonstrated that the neuropharmacological activities of β-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of β-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of β-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500- 750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of β-CBP. Conclusion: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of β-CBP in female Swiss mice.


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