Social isolation in prairie voles induces behaviors relevant to negative affect: toward the development of a rodent model focused on co-occurring depression and anxiety

Recent evidence suggests substantial overlap between mood and anxiety disorders, both in clinical presentation and associated features. A theoretical framework to account for this overlap focuses on negative affectivity, defined as the disposition to experience negative emotional states, including fear, sadness, and guilt. This model has been successful in explaining the co-occurrence of depressive and anxiety disorders in humans. As a next step, development of an animal model focused on both depression- and anxiety-relevant behaviors may advance understanding of depression-anxiety symptom overlap, relations of these disorders with associated medical conditions and responses to treatment. This study was designed to investigate inducible and quantifiable depression- and anxiety-like behaviors in prairie voles (Microtus ochrogaster). Adult, female prairie voles were exposed to 4 weeks of social pairing (control) or isolation, an established stressor for socially monogamous mammals (including humans). Operational measures of depression (sucrose intake and behaviors in the forced swim test), anxiety (behaviors in the elevated plus maze), and aggression (responses to an unrelated prairie vole pup) were investigated. Social isolation induced a progressive decline in sucrose intake and increased immobility time during the forced swim test. Social isolation also decreased the amount of time spent in the open arms of the elevated plus maze, and increased pup-directed attack behavior. The current findings suggest that isolation induces behaviors reflecting elevated negative affect. These results may provide a foundation for creating a rodent model to examine the mechanisms underlying comorbid mood and anxiety disorders.     

Antidepressant-like actions of minocycline combined with several glutamate antagonists

This study tested the potential antidepressant activity of minocycline alone or combined with two traditional antidepressant drugs or several glutamate receptor antagonists, using the time sampling method in the forced swimming test. Results showed that: desipramine (10.0 mg/kg, P<0.05; 15.0 mg/kg, P<0.05), minocycline (60.0 mg/kg, P<0.05; 80.0 mg/kg, P<0.05) and EMQMCM (1.5 mg/kg, P<0.05; 2.0 mg/kg, P<0.05), reduced immobility by increasing climbing. Fluoxetine (20.0 mg/kg, P<0.05; 25.0 mg/kg, P<0.05) reduced immobility by increasing swimming. MTEP (5.0 mg/kg, P<0.05; 10.0 mg/kg, P<0.05) and dizolcipine (1.0 mg/kg, P<0.05; 1.5 mg/kg, P<0.05) reduced immobility by increasing swimming and climbing. Combination experiments showed that a subthreshold dose of minocycline (50.0 mg/kg) synergized the antidepressant-like actions of subthreshold doses of: desipramine (5.0 mg/kg; P<0.05), EMQMCM (0.6 mg/kg; P<0.05), MTEP (2.5 mg/kg; P<0.05) and dizolcipine (0.5 mg/kg; P<0.05). In conclusion, minocycline produced antidepressant-like actions in the FST and subthreshold dose of minocycline combined with subthreshold dose of desipramine and several glutamate receptor antagonists and produced antidepressant-like actions.     

Involvement of the adenosine A1 and A2A receptors in the antidepressant-like effect of zinc in the forced swimming test

It was previously shown that the acute administration of zinc chloride elicits an antidepressant-like effect in the mouse forced swimming test (FST). We have also shown that the activation of adenosine A₁ and A_2A receptors produces an antidepressant-like effect in FST. Thus, this study investigated the involvement of adenosine receptors in the antidepressant-like effect of zinc in the FST. The antidepressant-like effect of ZnCl₂ (30 mg/kg, i.p.) in the FST was prevented by the pretreatment of animals with caffeine (3 mg/kg, i.p., a non-selective adenosine receptor antagonist), DPCPX (2 mg/kg, i.p., a selective adenosine A₁ receptor antagonist) or ZM241385 (1 mg/kg, i.p., a selective adenosine A_2A receptor antagonist), administered at doses that per se produced no anti-immobility effect. Moreover, the treatment of mice with CHA (0.05 mg/kg, i.p., a selective adenosine A₁ receptor agonist), DPMA (0.1 mg/kg, i.p., a selective adenosine A_2A receptor agonist) or dipyridamole (0.1 µg/site, i.c.v., an adenosine transporter inhibitor) was able to potentiate the action of sub-effective doses of ZnCl₂. Taken together, the results suggest that the antidepressant-like effect of zinc in the mouse FST might involve a direct or indirect activation of adenosine A₁ and A_2A receptors.     

Antidepressant-like effect of the novel thiadiazolidinone NP031115 in mice

Glycogen synthase kinase-3beta (GSK-3beta) is an enzyme that phosphorylates glycogen synthase, thereby inhibiting glycogen synthesis. Besides this role, it is now believed that this enzyme plays an important role in the pathophysiology of many brain diseases including depression. Some inhibitors of this enzyme have shown antidepressant effects in animal models. This study investigated the effects of a novel thiadiazolidinone NP031115, a putative GSK-3beta inhibitor, and the well-established GSK-3beta inhibitor AR-A014418 in the mouse forced swimming test (FST), a model widely used to evaluate antidepressant activity. We found that NP031115 had an IC50 of 1.23 and 6.5 microM for GSK-3beta and GSK-3alpha, respectively. NP031115 (0.5 and 5 mg/kg, i.p.), in a way similar to imipramine (15 mg/kg, i.p), fluoxetine (32 mg/kg, i.p), AR-A014418 (9 mg/kg, i.p.), and rosiglitazone (5 microg/site, i.c.v.), significantly reduced immobility time in the FST. NP031115 at the higher dose and AR-A014418 (9 mg/kg, i.p.) reduced locomotion in the open-field test. Rosiglitazone (30 microM), AR-A014418 (1 microM), PG(J2) (10 microM), and NP031115 (1, 10 and 25 microM) activate PPARgamma in CHO transfected cells. GW-9662 (10 microg/site, i.c.v, a PPARgamma antagonist) administered 15 min before NP03115 (5 mg/kg, i.p.) or co-administered with rosiglitazone (5 microg/site, i.c.v.) prevented the antidepressant-like effect of these drugs in the FST. The results of this study show that NP031115 can exhibit an antidepressant effect, likely by inhibiting GSK-3beta and enhancing PPARgamma activity.     

Central nervous system depressant activity of an ethyl acetate extract from Ipomoea stans roots

Ipomoea stans Cav., popularly known as "tumbavaqueros", is a plant widely used in Mexico for the treatment of epileptic seizures and nervous disorders. This work researched the action of the ethyl acetate extract from the root of I. stans (IS-EAE) on the central nervous system (CNS). The administration of IS-EAE (2.5 and 5.0 mg/kg, i.p.) produced an anxiolytic effect in mice. This extract (20.0 and 40.0 mg/kg, i.p.) significantly reduced spontaneous motor activity. 2.5, 5.0, 10.0, and 20.0 mg/kg of IS-EAE protected mice against pentylenetetrazole-induced convulsions and increased the hypnotic effect induced by pentobarbital. The administration of IS-EAE was able to increase the release of GABA in brain cortex of mice. These results suggest that IS-EAE possess anxiolytic and anticonvulsant effects, and could have potential sedative effect, probably through a GABAergic system. The extract did not show antidepressant effects on mice exposed to forced swimming test.     

Antidepressant activity of some Hypericum reflexum L. fil. extracts in the forced swimming test in mice

We previously reported that oral administration of the methanol extract obtained from the aerial part in blossom of Hypericum reflexum L. fil. was active in the tetrabenazine and forced swimming test. In the present study, the effect of the aqueous, butanol and chloroform fractions obtained from the methanol extract of this species on the central nervous system was investigated in mice, particularly in animal models of depression. Antidepressant activity was detected in the butanol and chloroform fractions of this species using the forced swimming test since both fractions induced a significant reduction of the immobility time, producing no effects or only a slight depression on spontaneous motor activity when assessed in a photocell activity meter. Moreover, these fractions did not alter significantly the pentobarbital-induced sleeping time. On the other hand, the chloroform fraction produced a slight but significant hypothermia and was also effective in antagonizing the ptosis induced by tetrabenazine. Furthermore, the butanol fraction produced a slight potentiation of the head twitches and syndrome induced by 5-HTP. Taken together, these data indicate that the butanol and chloroform fractions from Hypericum reflexum possess antidepressant-like effects in mice, providing further support for the traditional use of these plants in the Canary Islands folk medicine against central nervous disorders.     

新生儿游泳护理模式初探

目的探讨新生儿游泳对新生儿期的生理、心理发育的影响。方法将520例新生儿随机分为实验组和对照组,各260例。对照组按常规护理,实验组除按常规护理外,每日增加新生儿游泳10min。并对新生儿一般情况,以及新生儿生理现象的表现程度进行比较。结果两组新生儿一般情况及生理现象表现程度的比较有显著性差异（P〈0.01）。结论新生儿游泳是一项切实可行,符合新生儿生理、心理发育的活动。     

Effect of Tao-Hong-Si-Wu-Tang,A Traditional Chinese Herbal Medicine Formula,on Physical Fatigue in Mice

Tao-Hong-Si-Wu-Tang (THSWT) is a famous traditional Chinese herbal medicine formula, which has traditionally been used in China for about one thousand years. The present study investigated the effect of THSWT on physical fatigue. 32 male mice were randomly divided into 4 groups with 8 in each group. All were administered orally and daily for 28 days. Group I received isotonic saline solution as control; Group II, III and IV obtained 5, 10 and 20ml/ kg body weight of THSWT solutions, respectively. After 28 days, the anti-physical fatigue effect of THSWT was evaluated by using a forced swimming test, along with the determination of blood lactic acid, blood urea nitrogen (BUN), liver glycogen and muscle glycogen contents. The data showed that THSWT could extend exhaustive swimming time of mice, as well as decrease the BLA and BUN contents and increase the liver glycogen and muscle glycogen contents. The results support that THSWT had anti-physical fatigue effect.     

Acute myo-inositol enhances swimming activity in goldfish

Summary. Inositol in concentrations of 1–4 Mm (but not the control condition: mannitol-glucose) administered in aquarium water showed enhancement of swimming activity of goldfish after acute treatment (5 hours). These data support similar findings in rats. These data suggest that inositol may enhance motor activity which may be of relevance in neuropsychiatric disorders. Future studies of the effects of lithium on this activity, and its potential reversal by inositol may shed light on the possible involvement of the phosphatidyl-inositol second messenger system in this behavior. Received December 15, 1998; accepted January 20, 1999     

罗汉果皂苷抗疲劳及耐缺氧作用

目的:考察罗汉果皂苷的抗疲劳、耐缺氧作用.方法:将小鼠随机分为空白组,模型组,阳性对照组(红景天胶囊570 mg· kg-1),罗汉果皂苷高剂量( 300 mg· kg-1),中剂量(150 mg·kg-1)及低剂量组(75 mg·kg-1).连续灌胃给药21 d后采用力竭游泳实验和常压耐缺氧实验,考察罗汉果皂苷对小鼠的抗疲劳和耐缺氧能力的影响,并测定服用罗汉果皂苷后肝糖原和肌糖原的变化,及运动后血尿素氮、血乳酸含量和乳酸脱氢酶活力的变化.结果:罗汉果皂苷显著延长小鼠力竭游泳时间(P＜0.05),150,75 mg·kg-1组小鼠耐缺氧存活时间显著延长(P＜0.05).服用罗汉果皂苷后,小鼠肝糖原和肌糖原含量均显著增加(P ＜0.001),运动后血尿素氮和乳酸生成显著减少(P ＜0.001),乳酸脱氢酶活性显著增强(P＜0.05).结论:罗汉果皂苷能显著增强小鼠的抗疲劳和耐缺氧能力,其作用可能与增加机体糖原储备和加速乳酸代谢有关.