Modulatory Effects of the Glucocorticoid and Opioid Systems on Anxiety-Related Behavior in Young and Mature Rats

Considering that there is limited information on interaction between age and effects of the opioid system and glucocorticoids in determination of the level of anxiety, we examined the influences of 1 mg/kg dexamethasone and 20 mg/kg RU486 (as an agonist and an antagonist of glucocorticoid receptors), and also of 5 mg/kg morphine and 20 mg/kg naloxone (as an agonist and an antagonist of the opioid system) on the anxiety level in young and mature male Wistar rats. The percentage of time in the open arms in the plus-maze test was evaluated as an index of anxiety behavior, and the percentage of number of entries in the closed arms was measured as an index of locomotor activity. The results showed that morphine (5 mg/kg) and dexamethasone (1 mg/kg) exerted anxiolytic effects in both young and mature rats, while only in young rats these agents reduced locomotor activity. RU486 could prevent the anxiolytic effect of morphine, and the anxiolytic effect of dexamethasone was inhibited by naloxone in young animals but this was not observed in mature rats. These results showed that there is an interactive effect between glucocorticoids and the opioid system in mediation of anxiety, and the respective events are age-dependent.Враховуючи недостатню інформацію щодо взаємних впливів глюкокортикоїдів та опіоїдної системи на поведінку та залежність відповідних ефектів від віку, ми вивчали впливи введення 1 мг/кг дексаметазону та 20 мг/кг RU486 (агоніста та антагоніста глюкокортикоїдних рецепторів), а також 5 мг/кг морфіну та 20 мг/кг налоксону (агоніста та антагоніста опіоїдної системи) на рівень тривожності в тесті підвищеного лабіринту у молодих та зрілих щурів-самців. Нормовані значення часу, проведеного у відкритих рукавах лабіринту, та аналогічні значення кількості входів до закритих рукавів розглядались як індекси рівня тривожності та інтенсивності локомоторної активності відповідно. Уведення 5 мг/кг морфіну та 1 мг/кг дексаметазону зумовлювали значні анксіолітичні ефекти як у молодих, так і у зрілих щурів; дані агенти істотно знижували локомоторну активність тільки у молодих тварин. RU486 міг усувати анксіолітичні ефекти морфіну. Анксіолітичний вплив дексаметазону гальмувався налоксоном у молодих щурів, але цього не спостерігалось у зрілих тварин. Такі результати свідчать про існування істотної взаємодії глюкокортикоїдів та опіоїдної системи в їх функції опосередкування рівня тривожності та про значну залежність відповідних ефектів від віку

Different Efficacy of Nanoparticle and Conventional ZnO in an Animal Model of Anxiety

As has been shown, trace element supplementation by zinc, e.g., in the form of zinc oxide (ZnO), can significantly influence the anxiety level. We investigated the effects of ZnO in the form of nanoparticles (NPs) in comparison with conventional ZnO (cZnO) in an animal model of anxiety. Adult male Wistar rats were divided into seven groups, control (receiving 0.9% saline) and six groups receiving 5, 10, and 20 mg/kg ZnO NPs and 5, 10, and 20 mg/kg cZnO. All drugs dispersed in 0.9% saline were injected i.p.; 30 min later, the anxiety level was estimated according to the results of the elevated plus maze test. ZnO NPs (5 mg/kg) and cZnO (10 and 20 mg/kg) significantly increased the normalized values of time spent in open arms (open arm time, OAT, %) in comparison with the control group (P < 0.05). This is indicative of the anxiolytic effects of these components; in addition, 20 mg/kg ZnO NPs reduced the intensity of locomotor activity (P < 0.05). The serum zinc concentration was increased manifold by anxiolytic doses of the components. All doses increased serum pH to 8.05-8.10 and kept this index constant for 24 h. These results indicate that the anxiolytic effect of ZnO NPs is much more intense than that of conventional ZnO, but the introduction of ZnO NP as a new drug for the treatment of anxiety disorders needs further investigationsЯк було показано, додавання мікроелементу цинку (наприклад, у формі окису цинку, ZnO) може істотно впливати на рівень тривожності. Ми досліджували вплив ZnO у формі наночасток (НЧ) порівняно зі стандартним ZnO (сZnO) на пов’язану з тривогою поведінку у щурів. Дорослі щури лінії Вістар були поділені на сім груп – контрольну групу (тварини отримували фізіологічний розчин) та шість груп щурів, котрі отримували 5, 10 та 20 мг/кг ZnOНЧ, а також 5, 10 та 20 мг/кг сZnO. Усі дисперговані у 0.9 %-му фізіологічному розчині препарати ін’єкували внутрішньоочеревинно; через 30 хв після ін’єкції рівень тривоги оцінювали згідно з результатами тесту піднятог

Вeta1-Adrenoreceptors of the CA1 Area Mediate Morphine Modified State-Dependent Memory in Rat

In our study, we investigated the effects of intra­CA1 microinjections of a selective b1­ adrenoreceptor antagonist, betaxolol, on state­dependent memory induced by morphine. A step­through passive avoidance task was used to assess memory retrieval. Male Wistar rats were bilaterally implanted with chronic cannulas in the CA1 regions of the dorsal hippocampus by stereotaxic surgery seven days before training. Each animal was tested 24 h after training to measure the step­through latency and the time spent in a dark chamber of the apparatus. Post-training intra-CA1 administrations of different doses of morphine (5 and 7.5 mg/kg, s.c.) decreased memory retrieval in the retention test (morphine­induced amnesia). The effect of post­training injections of 7.5 mg/kg morphine on retrieval was reversed by pre­test injection of the same dose of morphine. This phenomenon is named morphine state­dependent memory. The results also showed that pre-test intra-CA1 microinjection of ineffective low doses of betaxolol (0.125 and 0.25 mg/rat) inhibited morphine­induced state­dependent memory retrieval. Taken together, our results suggest that the CA1 may be potentially critical for morphine state­dependent memory, and the b1­adrenergic receptor mechanism(s) interact with the opioidergic system in the modulation of this type of memory in the CA1.У нашій роботі ми досліджували впливи мікроін’єкцій селективного антагоніста b1­адренорецепторів бетаксололу в ділянку CA1 гіпокампа на формування залежної від стану пам’яті, індукованої ін’єкціями морфіну. Для оцінки ефективності здобування пам’ятних слідів використовували тест пасивного уникання. Самцям щурів лінії Вістар стереотаксично імплантували канюлі в ділянку CA1 дорсального гіпокампа за сім днів до тренування. Кожну тварину тестували через 24 год після тренування з вимірюванням латентного періоду уникання та тривалості перебування у темному відсіку тест­установки. Підшкірне введення 5 або 7.5 мг/кг морфіну після тренування послаблювало збереження пам’ятних слідів у відповідному тесті (індукована морфіном амнезія). Ефекти ін’єкцій 7.5 мг/кг морфіну після тренувань спотворювалися внаслідок ін’єкцій морфіну в тій самій дозі, виконаних перед тестом. Цей феномен кваліфікується як модифікація залежної від стану пам’яті під впливом морфіну. Як показали результати наших дослідів, мікроін’єкції в ділянку CA1 малих (неефективних) кількостей бетаксололу (0.125 або 0.25 мкг на тварину) послаблювали збереження індукованих морфіном модифікацій залежної від стану пам’яті. У цілому наші результати дозволяють вважати, що ділянка CA1 є критичною для формування модифікованої морфіном залежної від стану пам’яті і що b1­адренергічні рецепторні механізми взаємодіють із опіоїдергічною системою в перебігу модуляції пам’яті цього типу у щурів

Effect of Fe2O3 Nanoparticles on Anxiety Behavior and Nociception in Adult Male Rat

Abstract: Background & Aims: Iron is an essential element for correct brain function. Iron deficiency changes some behaviors such as anxiety and nociception. Recently, nano-iron, Ferric or ferro oxide (nano-Fe2O3 or Fe3O4), are used in various applications in agriculture, industry and medicine, but their effects on the heath and behavior is not clear. In this study, the effects of Fe2O3 nanoparticles on animal models of anxiety and nociception were investigated. Methods: Adult male Wistar rats (mean weight: 200-250 g) were used in 12 groups: 3 control groups (receiving saline 0.9%) and 9 groups received nano-Fe2O3 in doses of 0.2, 1 and 5 mg/kg, intraperitoneally. Elevated plus maze apparatus and hot-plate and tail-flick tests were used to evaluate anxiety and nociception, respectively. Data were analyzed by one-way ANOVA and post hock least significant difference (LSD) and P < 0.05 used as significant level. Results: Fe2O3 nanoparticles with dose addition increased open arm time percent (OAT%) (P<0.05). Locomotor activity, just in dose of 5 mg/kg, increased pain delay time in both hot-plate (P<0.01) and tail-flick (P<0.01) tests. Conclusion: Acute administration of Fe2O3 nanoparticle decreases anxiety behaviors in elevated plus maze and increases an acute pain threshold in both hot-plate and tail-flick tests in rats. Keywords: Anxiety, Pain, Fe2O3 nanoparticle, Ra

Role of endogenous opioids in nociception among male and different phases of the mice estrous cycle

Background: Sexual hormones can change nociception in males and females. There are few information about the role of sex hormones on nociception. The aim of this study was to evaluate the effect of endogenous opioids on nociception in male mice compared with female mice during different phases of the estrous cycle (proestrus, estrus, metestrus and diestrus).Materials and Methods: In this study, adult male and female mice (in different phases of estrous cycle (weighing 30±3gr were assigned to the control group, vehicle and naloxone (3mg/kg, i.p.) groups. In all groups analgesia time was evaluated by hotplate test. Results: Analgesia time in diestrus phase of control and vehicle groups of female rats was more than the other phases and different from the estrus phase (

Evaluation of analgesic and anti-inflammatory effect of nanoparticles of magnesium oxide in mice with and without ketamine

Abstract. -OBJECTIVES: According to importance and increasing application of nanoparticles and their toxicity, the identification effects of nanoparticles on physiological systems are essential. Some studies show magnesium has analgesic effect in some pain models but this evaluation was not carried on nano-magnesium oxide (MgO). Thus, present study was designed to evaluation effect of Mgo nanoparticles alone and in combination with ketamine on two pain and inflammation model in mice. MATERIALS AND METHODS: At this study, adult male mice was used which had 29±3 gram weight. Formalin and acetic acid tests were carried. Acetic acid (1%) was intraperitoneally injected 0.3ml and the abdominal writhing was counted from 10 to 30 minutes after it. Formalin (2.5%) was injected 0.04 ml/mouse subcutaneously in plantar site of mice. The time of licking was cumulatively measured 0-5 (acute phase) and 15-25 (chronic phase) minutes later. Control (negative control), ketamine (0.1 mg/kg), MgO nanoparticles (5 and 10 mg/kg), conventional MgO (5 and 10 mg/kg) and ketamine with conventional and nanoparticles MgO groups were studied in both tests. RESULTS: Mean of writhing was significantly decreased by all drugs with comparison to control group (p = 0.0001). This decreasing was significant between conventional and nanoparticle MgO. The time of licking at both acute and chronic phases of formalin test was significantly decreased by all drugs with comparison to control group. However, this mean had significant difference with MgO nanoparticles. CONCLUSIONS: It seems that the nano-MgO induces analgesic and anti-inflammatory effects through central and peripheral mechanisms at experimental formalin and acetic acid testes and potentiates effect of ketamine

Comparison of the Effects of Pre-training Administration of Zinc Oxide and ‎Zinc Oxide Nanoparticles on Long-term Memory of Adult Male Mice

BACKGROUND AND OBJECTIVE: Zinc oxide nanoparticles are one of the most widely used nanoparticles in fields of industry, medicine, pharmaceutical sciences, cosmetics, and nutrition. Multiple studies have demonstrated the negative effects of zinc oxide nanoparticles on the nervous system, while others have revealed their enhancing effects on the activity of nerve cells, involved in memory processes. The aim of this study was to compare the effects of zinc oxide nanoparticles and zinc oxide on long-term memory of mice. METHODS: In this experimental study, 49 NMRI adult male mice, with the mean weight of 25±5 g, were randomly divided into seven groups, each consisting of seven mice: control group, three treatment groups receiving zinc oxide nanoparticles (1, 2.5, and 5 mg/kg of  zinc oxide nanoparticles, respectively), and three treatment groups receiving zinc oxide (1, 2.5, and 5 mg/kg of zinc oxide, respectively). Intraperitoneal injections were performed before training (electric shock). Passive avoidance memory of mice was evaluated, using the Step-Down device. The latency time to descend the platform was regarded as an indicator of memory on days 1, 3, and 7 following training. FINDINGS: Pre-training administration of zinc oxide nanoparticles and zinc oxide at a dose of 2.5 mg/kg yielded no effects on the motor activity of mice. However, a significant decline was reported in the latency time to descend the platform on days 1, 3, and 7 following training (58±17, 45±13, and 39±14 in the zinc oxide group and 93±18, 62±12, and 14±3 in the nano zinc oxide group, respectively) (p<0.01) however, the dosage of 5 mg/kg had less significant short-term effects (130±38, 49±14, and 68±10 in the zinc oxide group and 132±46, 41±13, and 58±24 in the nano zinc oxide group, respectively). Also, the dosage of 1 mg/kg was almost ineffective. CONCLUSION: The results showed that weakened long-term memory, caused by zinc oxide administration, is not influenced by the size of particles