Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats

Rationale: There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in central physiological mechanisms. NO is synthesized from l-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-d-aspartate (NMDA) receptors by excitatory amino acids. NMDA receptor antagonists also produce antidepressant-like actions in preclinical models. Objective: In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (15, 30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined. Methods: The Porsolt forced swimming test (FST) has been used as a test for screening new antidepressant agents. Results: 7-NI dose-dependently decreased the immobility time in FST, but produced no significant change in locomotor activity in naive rats. Neither l-arginine, nor d-arginine (100 mg/kg) affected the immobility time in the FST or revealed any effect on locomotion. l-Arginine but not d-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time. Conclusion: Our findings suggest that NO might be an important modulator of depression in rats. Received: 3 June 1999 / Final version: 30 September 1999     

Antidepressant-like effect of nicotinamide adenine dinucleotide in the forced swim test in rats

Nicotinamide adenine dinucleotide (NADH), a cosubstrate for energy transfer in the oxidative phosphorylation, has supposedly beneficial effects on central nervous system (CNS)-related diseases, e.g., shown in an open study with depressive patients. To our knowledge there are no data concerning the efficacy of NADH in animal tests. Acute effects of NADH and the precursor nicotinamide, compared to controls and the antidepressants desipramine and fluoxetine, were examined in the forced swim test (FST) in Wistar rats. NADH, but not nicotinamide, reduced immobility and increased swimming behaviour in the FST, with a minimum effective dose of 5 mg/kg. NADH-induced behavioural profile was similar to fluoxetine, but different from desipramine. Since NADH did not induce hyperlocomotion but even decreased motor activity in the open field test, the antidepressant-like effect cannot be attributed to an increase in motor activity. These data support an antidepressant potential of NADH.     

Beneficial effect of hyperbaric oxygen pretreatment on lipopolysaccharide-induced shock in rats

1. We investigated the effect of hyperbaric oxygenation (HBO2) pretreatment on the production of exhaled nitric oxide (ENO) and the expression of lung inducible nitric oxide synthase (iNOS) by Escherichia coli lipopolysaccharide (LPS)-induced shock in an experimental rat model. 2. Rats were randomized into four groups, anaesthetized, mechanically ventilated with room air and infused with normal saline (2 mL/h) through the jugular vein for 5 h. Group 1 (NS) received only normal saline. Group 2 (HBO2-NS) was pretreated with HBO2 at 2.8 absolute atmospheres for 2 h and then received normal saline. Group 3 (LPS) received LPS, 20 mg/kg, i.v., bolus. Group 4 (HBO2-LPS) was pretreated with HBO2 for 2 h, followed by LPS. 3. Arterial blood gases, blood pressure, blood pH and ENO production were measured every 30 min. Plasma nitrite/nitrate (NOx) concentrations were assessed at the beginning (baseline) and at the end of the study. Lung myeloperoxidase (MPO) activity, iNOS expression and histological scores were measured for the evaluation of lung injury. 4. Administration of LPS was associated with decreased blood pressure and pH, increased ENO production, plasma NOx concentrations, lung iNOS expression and MPO activity. 5. Pretreatment with HBO2 significantly alleviated the LPS-induced hypotension, acidosis and decreased ENO production, plasma NOx concentrations, lung MPO activity and expression of iNOS. Hyperbaric O2 had no effect on control rats. 6. Our data show that HBO2 pretreatment has beneficial haemodynamic effects in rats with endotoxin shock. The beneficial effects of HBO2 may be partially mediated by decreased ENO production via reduced LPS-induced lung iNOS expression.     

Antidepressant-like effect of ethanol revealed in the forced swimming test in Sardinian alcohol-preferring rats

  Rationale: A large body of evidence indicates high comorbidity between depression and alcohol abuse. The self-medication hypothesis proposes that depressed subjects may abuse ethanol because it reduces the symptoms of depression. The present study evaluated whether ethanol may exert an antidepressant-like action in genetically selected alcohol-preferring rats, either Sardinian alcohol-preferring (sP) or Marchigian Sardinian alcohol-preferring (msP) rats, and for comparison in Sardinian alcohol-non-preferring (sNP) rats. Methods: The forced swimming test (FST) was used to evaluate the antidepressant-like action of ethanol; in this test the effect of ethanol ingestion on the immobility time was determined. Results: Ethanol-naive sP rats exhibited a longer period of immobility in comparison to sNP rats. Both in ethanol-naive sP and msP rats, voluntary ethanol drinking reduced the immobility time. A similar effect was obtained when repeated (five or nine) intragastric administrations of 0.7 g/kg ethanol were given during the 24 h prior to the test in msP and in sP, but not in sNP rats. Desipramine, like ethanol, sharply reduced immobility at doses of 5 or 20 mg/kg, given 3 times in the 24 h before the test in msP rats. The reduced immobility induced by ethanol in msP rats was apparently not the consequence of a general motor activation, because 9 IG administrations of ethanol, 0.7 g/kg, failed to alter locomotor activity in the open field test. Moreover, blood alcohol levels and rectal temperature of msP, sP and sNP after IG ethanol administration were not statistically different. Conclusions: The present results provide evidence for an antidepressant-like action of ethanol in sP and msP rats and suggest that this action may contribute to sustain their high ethanol drinking. Received: 3 August 1998 / Final version: 22 December 1998     

高压氧对重度颅脑外伤偏瘫的疗效观察

目的探讨高压氧对重度颅脑外伤偏瘫的疗效。方法将本院收治的64例重度颅脑外伤后偏瘫患者,按照自愿随机的原则分为观察组和对照组,每组各32例。对照组给予颅脑外伤常规治疗和康复治疗。观察组在对照组的基础上给予高压氧辅助治疗。观察两组的疗效。结果观察组患者的总有效率为90.625%,对照组为78.125%,两组间比较差异有统计学意义。观察组治疗后MBI评分为（70.3±15.2）分,与对照组的（60.1±15.4）分比较,差异有统计学意义;观察组治疗后上下肢FMA评分分别为（46.2±14.9）分、（34.3±9.8）分,与对照组的（31.5±14.9）分、（24.5±4.9）分比较,差异有统计学意义。结论重型颅脑损伤患者给予高压氧辅助治疗治愈率高,能明显提高患者的生活质量。     

Inactivation of Gi proteins induces an antidepressant-like effect in the mouse forced-swimming test

The effect of Gi protein inactivation was evaluated in an animal model of depression, the mouse forced swimming test. Animals were i.c.v. injected with pertussis toxin (PTX) or with antisense oligodeoxynucleotides directed against the alpha subunit of each Gi-protein subtype (anti-Gi alpha(1), anti-Gi alpha(2), anti-Gi alpha(3), anti-Go alpha(1), anti-Go alpha(2)). The administration of PTX (0.25 micro g per mouse i.c.v.) produced an increase in the mobility time. Similarly, anti-Gi alpha(2) (25 micro g per mouse i.c.v.), anti-Gi alpha(3) (25 micro g per mouse i.c.v.), anti-Go alpha(1) (12.5-25 micro g per mouse i.c.v.) and anti-Go alpha(2) (12.5-25 micro g per mouse i.c.v.) increased the mobility time. The antidepressant-like effect obtained was similar to that produced by amitriptyline and clomipramine. By contrast, pretreatment with anti-Gi alpha(1) (3.12-25 micro g per mouse i.c.v.) never modified the mobility time in comparison with control animals. At the highest effective doses, none of the compounds used impaired motor coordination (rota rod test), nor modified spontaneous motility and inspection activity, (hole board test). These results indicate the involvement of Gi(2), Gi(3), Go(1), and Go(2), but not Gi(1), protein subtypes in the transduction mechanism responsible for the induction of an antidepressant-like effect in the mouse forced swimming test.     

Antidepressant-like effect of Cordyceps sinensis in the mouse tail suspension test

Cordyceps sinensis (CS) has been known as a component of traditional medicines that elicit various biological effects such as anti-fatigue, immunomodulatory, and hypoglycemic actions. Since it has been well-established that fatigue is closely related to depression, we used the tail suspension test (TST) in mice to examine the antidepressant-like effects of hot water extract (HWCS) and supercritical fluid extract (SCCS) of CS. Immobility time in the TST was reduced by administration of SCCS (2.5-10 ml/kg, p.o.) dose-dependently though it was not reduced by treatment with HWCS (500-2000 mg/kg, p.o.). Neither HWCS nor SCCS altered locomotor activity in the open field test, excluding the possibility that the effect of SCCS is due to activation of locomotion. Pretreatment with prazosin (an adrenoreceptor antagonist) or sulpiride (a dopamine D2 receptor antagonist) reduced the effect of SCCS on the immobility time. In contrast, pretreatment with p-chlorophenylalanine (p-CPA, a serotonin synthesis inhibitor) did not alter the anti-immobility effect of SCCS. The last finding is consistent with an additional observation that SCCS had no effect on head twitch response induced by 5-hydroxy-L-tryptophan in mice. Taken altogether, these results suggest that SCCS may elicit an antidepressant-like effect by affecting the adrenergic and dopaminergic systems, but not by affecting the serotonergic system.     

抗抑郁剂慢性给药对强迫游泳大鼠下丘脑c-Fos蛋白表达水平的下调作用

应用c-Fos蛋白免疫组织化学定位观察的方法, 在强迫游泳大鼠抑郁模型上, 观察地昔帕明(5, 20 mg·kg^-1), 吗氯贝胺 (10, 40 mg·kg^-1)和氟西汀 (5, 20 mg·kg^-1) 慢性给药 (ip 每日1次, 连续7 d)对大鼠游泳不动时间和下丘脑核团c-Fos蛋白表达水平的影响. 结果表明: 强迫游泳可使大鼠下丘脑多个核团的c-Fos蛋白表达水平明显升高, 而地昔帕明, 吗氯贝胺, 氟西汀明显缩短强迫游泳大鼠的不动时间, 并选择性地使强迫游泳诱导增加的下丘脑室旁核Fos样免疫阳性神经元数目明显减少. 提示下丘脑室旁核可能是介导抗抑郁剂抑制大鼠绝望行为的中枢部位之一. Fos蛋白可能是不同类型抗抑郁剂共同的受体后信号转导物质.     

Potentiation by TRH of the effect of imipramine on the forced-swimming test.

Discovery of the potentiation of thyrotropin releasing hormone (TRH)-induced hyperthermia in mice by antidepressants which activate alpha-adrenergic systems instigated investigation of other relations between TRH and antidepressants. For this study the forced-swimming test using mice was chosen since this test is more sensitive for selection of antidepressants which modify catecholaminergic systems than for those affecting 5-hydroxytryptaminergic systems. The effects of imipramine were potentiated by TRH. The involvement of alpha-adrenergic systems was then investigated in this effect since it is already known that these systems are directly implicated in the potentiation of TRH-induced hyperthermia by some antidepressants. Then the involvement of opiate systems was investigated since endogenous opiates are implicated in the action of some antidepressants, and some interactions between TRH and opiate systems are known to exist. TRH made effective a completely inactive dose of imipramine as small as 2 mg kg-1 (i.p.) or 1 microgram per mouse (i.c.v.). Pretreatment by both alpha 1- and alpha 2-adrenoceptor antagonists (phenoxybenzamine, 8 mg kg-1 i.p.; phentolamine, 4 mg kg-1 i.p.) or by a alpha 1-adrenoceptor antagonist (prazosin, 2 mg kg-1 i.p.) did not prevent this potentiation. In contrast the alpha 2-adrenoceptor antagonist (Yohimbine, 2 mg kg-1 i.p.) blocked the TRH effect. The imipramine potentiation by TRH was blocked by pretreatment with an opiate antagonist (naloxone, 1 mg kg-1 i.p.) and the potentiation was decreased in morphine-tolerant mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antidepressant-like effect of different estrogenic compounds in the forced swimming test.

The present study evaluated the possible antidepressant-like action of the natural estrogen 17beta-estradiol (E(2), 2.5-10 microg/rat), the synthetic steroidal estrogen ethinyl-estradiol (EE(2), 1.25-10.0 microg/rat), and the nonsteroidal synthetic estrogen, diethyl-stilbestrol (DES, 0.25-1.0 mg/rat) in ovariectomized adult female Wistar rats using the forced swimming test (FST). The behavioral profile induced by the estrogens was compared with that induced by the antidepressants fluoxetine (FLX, 2.5-10 mg/kg) and desipramine (DMI, 2.5-10 mg/kg). In addition, the temporal course of the antidepressant-like action of the estrogenic compounds was analyzed. FLX and DMI induced an antidepressant-like effect characterized by a reduced immobility and increased swimming for FLX and decreased immobility and increased climbing for DMI. Both E(2) and EE(2) produced a decrease in immobility and an increase in swimming, suggesting an antidepressant-like action. DES did not affect the responses in this animal model of depression at any dose tested. The time course analysis of the actions of E(2) (10 microg/rat) and EE(2) (5 microg/rat) showed that both compounds induced an antidepressant-like effect observed 1 h after their injection lasting for 2-3 days.     

立即高压氧治疗对大鼠局灶性脑缺血后脑水含量的影响

目的探讨立即高压氧(HBO)治疗对大鼠局灶性脑缺血后脑水含量的影响。方法应用线栓法制作大鼠局灶性脑缺血模型。将70只健康Wistar大鼠随机分为假手术组、缺血对照组和高压氧治疗组(HBO组)。各组大鼠均于缺血后2h再灌注,24h后断头取脑,观察各组大鼠脑组织含水量,并记录大鼠死亡率及平均存活时间,进行组间比较。结果与对照组相比,HBO治疗能减少脑水含量,降低死亡率,差异具有统计学意义(P<0.05);但HBO治疗并没有明显延长动物的平均存活时间。结论脑缺血后立即给予HBO治疗能减少脑水含量,减轻脑水肿,降低死亡率。     

高压氧综合治疗突发性耳聋的疗效观察

目的：探讨高压氧综合治疗突发性耳聋的疗效。方法：A组56例突发性耳聋患者行高压氧加药物联合治疗;B组53例突发性耳聋患者仅行药物治疗。结果：A组的有效率为89．1％,优于对照组的75．4％（P〈0．05）。听力损失〉70dB者的疗效（77．3％）低于听力损失45-70dB（95．2％）者。A组耳鸣治疗有效率（81．6％）高于B组（62．2％）,P〈0．05。结论：高压氧加药物联合治疗突发性耳聋疗效肯定,无明显不良发应,为临床治疗突发性耳聋较理想的方案。     

Antidepressant-like effect of combined treatment with selective sigma receptor agonists and a 5-HT1A receptor agonist in the forced swimming test in rats

The interaction between the selective sigma (sigma) receptor agonists and 8-OH-DPAT, a serotonin (5-HT)(1A) receptor agonist, was examined in the forced swimming test in rats. The results indicate that joint administration of DTG (5 mg/kg) or SA4503 (3 mg/kg), the selective sigma(1)/sigma(2)- or sigma(1)-receptor agonists, respectively, and 8-OH-DPAT (0.1 or 0.3 mg/kg) induces an antidepressant-like effect. The doses of sigma agonists and 8-OH-DPAT used in the study were inactive per se in this model. The effect of DTG and 8-OH-DPAT co-administration was partly counteracted by WAY 100635 (0.1 mg/kg) as well as by BD 1047 (3 mg/kg), a 5-HT(1A) and sigma(1) receptor antagonists, respectively, suggesting the involvement of both receptor types in the anti-immobility effect in rats.     

Antidepressant-like effects of N-acetyl-L-cysteine in rats

Oxidative stress disturbances have been reported in depressed patients and in animals submitted to stress. Recent evidence suggests that antidepressants may have antioxidant properties. However, the therapeutic potential of antioxidants as antidepressant drugs has not been systematically investigated. Therefore, this study tested the hypothesis that N-acetyl-L-cysteine (NAC), a cysteine prodrug with powerful antioxidant activity, would possess antidepressant-like properties in the forced swimming test. Male Wistar rats were subjected to 15 min of forced swimming and immediately afterward, 5, and 23 h later received intraperitoneal injections of NAC (5, 15, 50, 150, and 250 mg/kg), imipramine, (15 mg/kg) or vehicle. One hour later they were submitted to the 5 min test swimming session, where immobility time was recorded. Independent groups of animals received the same treatments and their exploratory activity was measured in an open arena for 5 min. NAC (at the doses of 15, 50, and 150 mg/kg) and imipramine induced a significant decrease in immobility time without changing exploratory behavior measured in an open arena. These results suggest that antioxidants such as NAC may have antidepressant effects.     

Decrease of immobility behavior in forced-swimming test and immune system enhancing effect of traditional medicine Gamisipjundaebo-tang

Gamisipjundaebo-tang (GSDBT) has been used for the purpose of development of physical strength. In the present study, we investigated the immune enhancing effect induced by GSDBT. We investigated the anti-immobility effect of GSDBT via a forced-swimming test and blood biochemical parameters related to fatigue, glucose, blood urea nitrogen, lactic dehydrogenase, creatine kinase, and total protein. GSDBT (0.1 and 1 g/kg) was orally administered to mice for 14 days. After 7 and 14 days, as assessed through a forced-swimming test, immobility time was decreased in the GSDBT-administrated group (0.1 and 1 g/kg) in comparison with the control group. In addition, after 8 days, the contents of glucose and lactate dehydrogenase in the blood serum were increased, and contents of blood urea nitrogen were decreased in the GSDBT-administrated group. After 15 days, the contents of glucose were increased, and the contents of lactate dehydrogenase and blood urea nitrogen were decreased in the GSDBT-administrated group. However, it had no effect on the elevation of creatine kinase and total protein level. We also investigated the effect of GSDBT on the production of cytokines in human T-cell line, MOLT-4 cells, and splenocytes. GSDBT significantly increased interferon (IFN)-gamma and interleukin (IL)-2 levels compared with the media control but did not affect IL-4. GSDBT increased the protein expression of IFN-gamma in MOLT-4 cells. These results suggest that GSDBT may be useful in immune function improvement and may also have antifatigue properties.     

Antidepressant-like effects of baclofen and LY367385 in the forced swim test in rats

Baclofen, an agonist of GABA(B) receptors and LY367385, an antagonist of mGluR(1a) receptors, given alone or jointly, reduced the immobility time in the forced swim test but only their separate administration enhanced motility in group of rats without hypoxia. Short-term hypoxia (2% O2, 98% N2, 4 min) did not change the activity of the rats in the forced swim test and it did robustly decrease the motility of these animals. LY367385 reduced the immobility time in the forced swim test but induced locomotion in rats subjected to hypoxia. The obtained results indicated that baclofen and LY367385 given alone or jointly induce an antidepressant-like effect in the forced swim test but only LY367385 possesses such activity in rats that had undergone hypoxia. Both tested ligands are involved in the motility of rats, however, LY367385 influences hypolocomotion hypoxia-induced.     

Effect of monoamine precursors on the forced-swimming test in mice

The antidepressant properties of monoamine precursors were evaluated by the forced-swimming test for mice developed by Porsolt et al. DOPA but not 5-hydroxy-tryptophan (5HTP) shortened immobility at doses that did not increase locomotor activity. Although l-threo-dihydroxyphenylserine (DOPS), an artificial norepinephrine (NE) precursor, did not change immobility in intact mice, DOPS significantly reduced immobility in mice pretreated with the selective NE neurotoxin DSP4. These results suggest possible antidepressant properties of DOPA and DOPS, the latter of which may act as an antidepressant in a certain NE-depleting condition.     

高压氧治疗糖尿病的临床疗效观察

目的探讨高压氧治疗糖尿病的临床疗效。方法将136例糖尿病患者随机分为观察组和对照组（各68例）,对照组给予基础治疗,观察组在对照组的基础上加用高压氧治疗。结果观察组疗效总有效率为92.6%,明显优于对照组的76.5%,两组总有效率比较差异有统计学意义（P〈0.05）;观察组治疗后FPG及2hPBG下降程度与对照组比较,差异均有统计学意义（P〈0.05）。结论应用高压氧辅助治疗糖尿病疗效显著,能够有效降低患者血糖,改善临床症状,值得推广。     

高压氧对大鼠肾缺血再灌注损伤的影响及其机制

目的:探讨高压氧对大鼠肾缺血再灌注损伤(IRI)的影响及其机制。方法:成年健康Wistar大鼠60只,随机分为4大组,正常对照组(n=6)、假手术组(n=18)、肾缺血再灌注组(IR组,n=18)和肾缺血再灌注+HBO治疗组(HBO治疗组,n=18)。后3组又按再灌注后1h、3h和5h各分为3个亚组,每个亚组大鼠6只。各组先切除右肾,取左肾研究。正常对照组切除右肾后立即切取左肾备用。假手术组不阻断左肾动脉,肾IR组和HBO治疗组则采用钳夹肾动脉法建立左肾缺血再灌注损伤模型。HBO治疗组:在肾缺血再灌注后0h、2h和4h时分别将大鼠置于动物实验用高压氧舱内治疗1h之后,治疗压力为2(Atmosphere absolute,ATA)(0.1MPa),舱内氧浓度在98%以上。各组分别于再灌注后1h、3h和5h时检测血中SCr、BUN、MDA和TNF-α的含量,并取左肾组织用于石蜡切片和HE染色、流式细胞术(Flow cytometry,FCM)行Amn-nexin V/PI双染法检测细胞凋亡以及电镜检查。结果:(1)在IR组,血中检测指标量显著高于同时点正常对照组和假手术组(P<0.05);在HBO治疗组,各指标在...