Repeated electroconvulsive stimuli have long-lasting effects on hippocampal BDNF and decrease immobility time in the rat forced swim test

Electroconvulsive therapy is considered an effective treatment for severe depression. However, the mechanisms for its long-lasting antidepressant efficacy are poorly understood. In the present study, we investigated changes of the immobility time in the forced swim test and brain-derived neurotrophic factor (BDNF) protein after withdrawal from 14-day repeated electroconvulsive stimuli (ECS, 50 mA, 0.2 s) in rats. Immobility time in the forced swim test was markedly decreased 6 h after withdrawal following 14-day ECS treatment. Thereafter, prolongation of the withdrawal period gradually diminished the decreasing effect of immobility time, but significant effects persisted for up to 3 days after the withdrawal. Locomotor activity in the open-field test increased 6 h after withdrawal from the ECS treatment, and the enhanced effect persisted for at least 7 days. The BDNF protein level in the hippocampus was markedly increased 6 h after the withdrawal, and remained high for at least 7 days. These findings provide further evidence that repeated ECS has long-lasting effect on increase in BDNF and locomotor activity and decrease in immobility time in the forced swim test.     

Effect of combined treatment with imipramine and metyrapone on the immobility time, the activity of hypothalamo-pituitary-adrenocortical axis and immunological parameters in the forced swimming test in the rat.

Major depression is frequently associated with the hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. The aim of the present study was to examine the effect of joint administration of metyrapone (50 mg/kg) and imipramine (5 and/or 10 mg/kg) on immobility time, plasma corticosterone concentration, the weight of spleens and thymuses and the proliferative activity of splenocytes in rats subjected to the forced swimming test--an animal model of depression. Metyrapone alone (50 mg/kg) reduced the immobility time of rats in the forced swimming test and decreased plasma corticosterone level, but did not change immunological parameters. Joint administration of metyrapone and imipramine (5 and 10 mg/kg) produced a more pronounced antidepressant-like effect than either of the drugs given alone. The forced swimming procedure significantly increased the proliferative activity of splenocytes, that parameter being reduced only by co-administration of metyrapone and imipramine. Joint administration of metyrapone and imipramine inhibited to a similar extend the corticosterone level as did treatment with metyrapone alone (about twofold); however, the plasma corticosterone level in animals treated with metyrapone and the higher dose of imipramine did not differ from the concentration of this steroid in control, not-stressed rats. The obtained results indicate that metyrapone potentiates the antidepressant-like activity of imipramine and exerts a beneficial effect on the stress-induced increase in plasma corticosterone concentration and the proliferative activity of splenocytes. These finding suggest that a combination of metyrapone and an antidepressant drug may be useful for the treatment drug-resistant depression and/or depression associated with a high cortisol level.     

The comparison of immobility time in experimental rat swimming models

Rat swimming models have been used in studies about stress and depression. However, there is no consensus about interpreting immobility (helplessness or adaptation) in the literature. In the present study, immobility time, glucose and glycogen mobilization, corticosterone and the effect of desipramine and diazepam were investigated in two different models: swimming stress and the forced swimming test. Immobility time was lower in swimming stress than in the forced swimming test. Both swimming models increased corticosterone levels in comparison with control animal levels. Moreover, swimming stress induced higher corticosterone levels than the forced swimming test did [F(2,14)=59.52; p<0.001]. Liver glycogen content values differed from one another (swimming stress相似文献   

Evidence that muscimol acts in the forced swimming test by activating the rat dopaminergic system

Muscimol as well as catecholaminergic drugs reduce immobility time in the forced swimming test. In view of the fact that GABAergic drugs may facilitate some brain catecholaminergic functions, we investigated as to whether or not muscimol would reduce immobility time through activation of catecholaminergic mechanisms. The effect of muscimol (2 mg/Kg i.p.) on reduction of immobility time was prevented by intraperitoneal alpha-methyl-para-tyrosine (250 mg/Kg i.p.), which reduces brain catecholamine content, haloperidol (0.5 mg/Kg) and sulpiride (100 and 50 mg/Kg), antidopaminergic drugs, and meta-chlorphenyl-piperazine (0.6 and 1.25 mg/Kg), a serotonergic agonist, but not by clonidine (0.1 mg/Kg), an alpha2-adrenoceptor agonist, d, 1-propranolol (5 mg/Kg), an antagonist of beta-adrenergic receptors, or subcutaneous prazosin (3 mg/Kg), an alpha1-adrenolytic drug. Our findings indicate that a) muscimol reduces immobility time by stimulating dopaminergic neurons and b) activation of the serotonergic system antagonizes muscimol effect.     

Effect of plasticity in hatching on duration as a precompetent swimming larva in the nudibranch Phestilla sibogae

Abstract. Plasticity in hatching can balance risks of benthic and pelagic development and thereby affect the extent of larval dispersal. Veligers of the nudibranch Phestilla sibogae hatched from their individual capsules if the encapsulated embryos were scattered from a torn gelatinous egg ribbon. Hatching occurred as early as day 4 at 23°–25°C. The early hatchlings lacked a propodium, swam, and were not yet competent to settle and metamorphose. Hatching may be induced by predation: crabs consumed egg ribbons, and a portunid crab, caught in the act of tearing an egg ribbon, scattered encapsulated embryos. Undisturbed egg masses hatched as late as 9–11 d at 23°–25°C, or as early as 8 d in a trial at 26°C. Late hatchlings had a well-developed propodium, and 20–100% metamorphosed within a day of exposure to the inducer from the nudibranch's coral prey. A few metamorphosed nudibranchs were found within hatching egg masses. Thus, the veligers can hatch so late that many are competent to metamorphose or so early that the obligate planktonic period can last 4 or more days. An attack by a predator means the benthic habitat is dangerous for the embryos, and swimming is presumably the safer option. In the absence of disturbance, the veligers hatch when ready or nearly ready to settle.     

Effect of neonatally injected ACTH and ACTH analogues on eye-opening of the rat.

Three-day old rats were injected subcutaneously either with natural purified pig ACTH (ACTH 1–39), ACTH 1–24, or ACTH analogues as long-acting zinc-phosphate preparations. ACTH 1–39, ACTH 1–24, ACTH 1–18, ACTH 1–16 accelerated the time of eye-opening, whereas an extract of corticosteroids produced $\text{in}$$\text{vitro}$ by excised adrenals of ACTH-treated three-day old rats was ineffective. Injections with ACTH on the twelfth day of life had no effect on eye-opening. It is concluded that a neonatal injection with ACTH or closely related analogues with markedly less corticotropic activity can accelerate the time of eye-opening. This effect is not mediated by the adrenal cortex. The sensitive period for it appears to be shortly after birth.     

Synthesis and antidepressant-like action of stereoisomers of imidobenzenesulfonylaziridines in mice evaluated in the forced swimming test

The present study describes the chemical synthesis and pharmacological evaluation of a new series of eleven compounds stereoisomers of imidobenzenesulfonylaziridines in the forced-swimming test (FST) in mice. The pharmacological results of these compounds show that six of them, given intraperitoneally, reduced the immobility time of mice evaluated in the FST, an antidepressant-like profile of action similar to imipramine, a well-known standard antidepressant drug used for comparison, without compromising the animals' motor performance. The putative antidepressant-like action demonstrated here indicates their viability for the development of new therapeutic options for the treatment of depression.     

Expression of stress-evoked analgesia, connected with activity of animals in a forced swimming test]

The influence of forced swimming on the development of stress-induced analgesia was studied in 35 SHR mice, 65 NMRI mice, and 23 white outbred male rats. Mice were subjected to swimming conditions (at a temperature of 11 degrees C) for a period of 4 minutes and rats for 6 minutes. Pain thresholds were measured by a footshock. It was shown that behavioral response to acute stress is associated with a change in the pain tolerance threshold: activity of an animal under test conditions positively correlated with stress-induced analgesia. The response to stress and parameters of stress-induced analgesia depend on the genetic factor and age, however, the correlation between the activity during exposure to stress and the extent of stress-induced analgesia conserves in all cases.     

Different effects of intracerebral and systemic administration of buspirone in the forced swimming test: involvement of a metabolite

Buspirone, a drug with high affinity for serotonin1A receptors, was studied for its ability to reduce rats' immobility in the forced swimming test when injected systemically or into the nucleus raphe dorsalis (DR). Between 0.1 and 10 mg/kg buspirone had no effect on rats' immobility when injected systemically as a single dose or as a 3-injection course during 24 hours. Direct injection of 1 and 5 mu/0.5 microliter buspirone in the DR significantly reduced the duration of immobility without changing rats' activity in an open field. The anti-immobility effect of 1 microgram/0.5 microliter buspirone in the DR was completely prevented by injecting 2.5 micrograms (-)-propranolol in the same area. Oral administration of 0.3-1.0 mg/kg 1-(2-pyrimidinyl)piperazine (1-PP), one of the main metabolites of buspirone, and 0.3-3.0 mg/kg s.c. idazoxan, two substances with alpha 2 adrenergic blocking properties, completely antagonized the effect of 0.25 mg/kg s.c. 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), an agent with selective affinity for serotonin1A receptors. The anti-immobility effect of an infusion of 1 microgram/0.5 microliter buspirone or 8-OH-DPAT in the DR was also antagonized by 1 mg/kg p.o. 1-PP. The results suggest that buspirone possesses potential antidepressant properties but its effects may be masked in certain tests by its metabolite, 1PP, through its alpha 2 adrenergic blocking activity.     

The selective glucocorticoid receptor antagonist CORT 108297 decreases neuroendocrine stress responses and immobility in the forced swim test

Pre-clinical and clinical studies have employed treatment with glucocorticoid receptor (GR) antagonists in an attempt to limit the deleterious behavioral and physiological effects of excess glucocorticoids. Here, we examined the effects of GR antagonists on neuroendocrine and behavioral stress responses, using two compounds: mifepristone, a GR antagonist that is also a progesterone receptor antagonist, and CORT 108297, a specific GR antagonist lacking anti-progestin activity. Given its well-documented impact on neuroendocrine and behavioral stress responses, imipramine (tricyclic antidepressant) served as a positive control. Male rats were treated for five days with mifepristone (10 mg/kg), CORT 108297 (30 mg/kg and 60 mg/kg), imipramine (10 mg/kg) or vehicle and exposed to forced swim test (FST) or restraint stress. Relative to vehicle, imipramine potently suppressed adrenocorticotropin hormone (ACTH) responses to FST and restraint exposure. Imipramine also decreased immobility in the FST, consistent with antidepressant actions. Both doses of CORT 108297 potently suppressed peak corticosterone responses to FST and restraint stress. However, only the higher dose of CORT 108297 (60 mg/kg) significantly decreased immobility in the FST. In contrast, mifepristone induced protracted secretion of corticosterone in response to both stressors, and modestly decreased immobility in the FST. Taken together, the data indicate distinct effects of each compound on neuroendocrine stress responses and also highlight dissociation between corticosterone responses and immobility in the FST. Within the context of the present study, our data suggest that CORT 108297 may be an attractive alternative for mitigating neuroendocrine and behavioral states associated with excess glucocorticoid secretion.     

Stress by forced swimming in the rat: effects of mianserin and moclobemide on GABAergic-monoaminergic systems in the brain

The stress caused by forced swimming in male rats provoked a decrease in brain NA levels without changes in DA and 5-HT content, MAO and GABAergic activity. Acute or chronic treatment with mianserin did not modify the decrease in NA concentration in the brain of stressed rats. Acute treatment with moclobemide (IMAO) did not modify the decrease in NA content caused by stress; chronic treatment blocked the decrease in NA content in stressed rats.     

Effect of forced swimming on the memory track retention in mice with various behavioral stereotypes

The effects of forced swimming on retrieval of the passive avoidance during its extinction were found to depend on aggressive and submissive behavior. In mice without generated behavioral stereotypes, swim stress applied before or after training stabilized retention of the memory trace retrieval. The similar improved influence of forced swimming on memory storage is revealed in submissive, but not aggressive mice. The increase of resistance against extinction under the swim stress can be connected to facilitation of emotional processes.     

Effect of the duration of a reproducible interval on reaction time in man

The dependence of reaction time (RT) of reproduction of presented standard intervals on their duration (100-5000 ms) was studied on 30 subjects. The intervals were limited by two electrocutaneous stimuli or two clicks and were presented both at random and at a gradual increase or decrease, with a step of 100 ms. They were reproduced by pressing a button. The RTs duration depended on the presented interval within the range from 100 to 2000 ms. Such scatter of the upper limit is due to differences in the methods of presentation of the material and to individual features of the subjects. A presence of two mechanisms of time intervals reproduction is suggested for such experimental conditions: the image of the standard interval might be created either after its presentation or in the process of its presentation. Correspondingly, the RT dependence on the interval duration is manifest in the first case and is absent in the second.     

The influence of the bronchodilatation test on the duration of forced expiratory tracheal noises in young men

The diagnostic efficiency of estimating the duration of forced expiratory noises under the conditions of bronchial obstruction has been shown. The objective of this study was to analyze the response of the forced expiratory noise duration to the bronchodilatation test with the β₂-agonist in the age- and genderhomogenous group of healthy volunteers and bronchial asthma patients selected as a model of variable bronchial obstruction. Two hundred and sixty young men (16–25 years old) were examined. It was shown that the prevailing type of response in bronchial asthma patients with spirometry confirmed bronchial obstruction was shortened forced expiratory noises. Furthermore, the degree of the shortening considerably depended on the severity of the background bronchial obstruction. The absence of a statistically significant response of the forced expiratory noise duration dominated among healthy volunteers (nonsmokers as well as smokers) and bronchial asthma patients without a spirometry confirmed bronchial obstruction. However, the shortened response occurred much more frequently in bronchial asthma patients than in healthy volunteers. The high specificity (86%) of the response as shortened forced expiratory noises to the β₂-agonist may be useful for diagnostics.     

Procognitive 5-HT6 antagonists in the rat forced swimming test: Potential therapeutic utility in mood disorders associated with Alzheimer's disease

Aims5-HT₆ receptor subtype is predominantly expressed in the brain, and preclinical evidence suggests its potential role in the cognitive function. Brain microdialysis studies demonstrated that 5-HT₆ antagonists enhance not only cholinergic but also monoaminergic neurotransmission, a property that may differentiate from acetylcholine esterase (AChE) inhibitors such as donepezil. In this study we compared the antidepressant-like effects of 5-HT₆ antagonists with donepezil to determine whether their different effects on monoamines are behaviorally relevant.Main methodsSelective 5-HT₆ antagonists (SB-399885 and SB-271046) and donepezil were evaluated in the rat forced swimming test since this is known to identify drugs such as antidepressants which can increase brain monoamine levels. Binding assay was undertaken by using [¹²⁵I]SB-258585 to measure brain 5-HT₆ receptor occupancy.Key findingsSystemic administration of SB-399885 (3 and 10 mg/kg, i.p.) and SB-271046 (10 and 30 mg/kg, i.p.) produced a significant reduction of immobility time in the rat forced swimming test with a similar profile in terms of 5-HT₆ receptor occupancy (62 and 96% for 3 and 10 mg/kg SB-399885 respectively; 56 and 84% for 10 and 30 mg/kg SB-271046 respectively). In contrast, donepezil (0.5 and 1 mg/kg i.p.) did not show any effects in this model.SignificanceThese data suggest that 5-HT₆ antagonists, at doses corresponding to those occupy central 5-HT₆ receptors, could have an antidepressive effect in humans. This may differentiate 5-HT₆ antagonists from AChE inhibitors with respect to the mood control in the symptomatic treatment of Alzheimer's disease.     

The striatum and the organization of forced swimming in rats

Prolonged repeated electric stimulation of rats striatum causes stable behavioural depression and reorganization of temporal dynamics of forced swimming. Simultaneously increases the depression index offered by us as ratio of the number of immobilization cycles shorter than 6 s to the total number of active swimming cycles. Striatectomy and amphetamine administration (1 mg/kg) uniformly change the rhythmic structure of swimming with an increase of animals general motor activity without change of the depression index. It is suggested to use striatal inactivation as a model of depression state.