BACKGROUND & AIMS: RATIONALE:Rats avidly consume standard off-the-shelf beer; however, the behavioural consequences of beer consumption in rodents have hardly been studied. OBJECTIVES:The present study examined the acute anxiolytic and ataxic effects of beer consumption in rats and the anxiogenic effects of withdrawal from free access to beer. METHOD:In experiment 1, male Wistar rats received 30 min access to "near-beer" each day (a malt beverage that looks and tastes like beer but which contains <0.5% ethanol). On the test day, for some rats, ethanol (either 2% or 4% v/v) was added to the near-beer to make it resemble standard (ethanol-containing) beer of "light" (2.5% beer) or full strength (4.5% beer). Immediately after this, rats were tested on their response to a predatory cue (a fabric collar that had been worn by a cat) and on an accelerating rotarod. In experiment 2, rats were trained in the same drinking paradigm as above and then tested on a further battery of anxiety tests. In experiment 3, rats were given continuous home cage access to either 4.5% beer or near-beer for 35 days. Half of the rats were then denied access to beer or near-beer for 24 h and then tested on the same anxiety test battery as in experiment 2. RESULTS:Rats drinking 4.5% beer approached a predatory cue significantly more than those given near-beer, indicating an anxiolytic effect. In experiment 2, rats drinking 4.5% beer displayed less anxiety-like behaviour in the elevated plus maze and emergence tests but not in the social interaction test. Rats given 4.5% beer fell off the rotarod significantly faster than rats given near-beer, indicating an ataxic effect. Rats previously given 4.5% beer drank significantly less near-beer the following day, suggesting a moderate aversion the day after beer consumption. In experiment 3, rats denied access to 4.5% beer showed significantly less social interaction and took longer to emerge into an open field than controls. CONCLUSION:These results are the first to our knowledge to show that rats will consume beer at levels that produce clear effects on anxiety and on motor co-ordination, and that will eventually produce behavioural signs of withdrawal.

背景与目标：

BACKGROUND & AIMS: :PD134308 and PD135158 are highly selective CCK-B receptor antagonists and were used to investigate the role of CCK-B receptors in aversive responding in rodent and primate models of anxiety. Both PD134308 and PD135158 were as effective as diazepam to antagonise aversive behaviour in the mouse light/dark discrimination test, in the rat social interaction and elevated X-maze tests, and in a marmoset 'human threat' model. However, the CCK-B antagonists were much more potent than diazepam and their effects were recorded over an extensive dose range. Furthermore, even at high doses, sedation or muscle relaxation was not observed and anxiogenesis was absent after withdrawal from a subchronic treatment. In contrast, withdrawal from drugs of abuse, diazepam, alcohol, cocaine and nicotine was associated with a withdrawal anxiogenesis that was completely prevented by PD134308 and PD135158. It is concluded that CCK-B receptors are involved in aversive-anxiety responding and that CCK-B receptor antagonists may provide a novel and improved approach to the treatment of anxiety and withdrawal from drugs of abuse.

背景与目标： : PD134308和PD135158是高度选择性的cck-b受体拮抗剂，用于研究cck-b受体在啮齿动物和灵长类动物焦虑模型中的厌恶反应中的作用。PD134308和PD135158在小鼠的光/暗辨别测试，大鼠的社交互动和X迷宫测试以及mar猴的 “人类威胁” 模型中均与地西epa一样有效地对抗厌恶行为。然而，cck-b拮抗剂比地西epa有效得多，并且在广泛的剂量范围内记录了它们的作用。此外，即使在高剂量下，也未观察到镇静或肌肉松弛，并且在从亚慢性治疗中退出后也没有焦虑发生。相反，从滥用药物，地西epa，酒精，可卡因和尼古丁的戒断与戒断焦虑有关，PD134308和pd135158完全阻止了戒断焦虑发生。结论是cck-b受体参与了厌恶性焦虑反应，cck-b受体拮抗剂可能为治疗焦虑和戒断滥用药物提供了一种新的改进方法。

BACKGROUND & AIMS: :The relevance of 5-HT1A and 5-HT2C receptors of the basolateral nucleus of the amygdala (BLA) in the mediation of anxiety-related defensive responses has long been acknowledged. Whereas strong evidence supports that activation of the latter receptors provokes anxiety, conflicting findings have been reported on the role played by the former binding site. In this study we further investigated the involvement of 5-HT1A receptors (5-HT1A-Rs) in the regulation of anxiety- and panic-related defensive behaviors. The results showed that intra-BLA injection of the 5-HT1A-R agonist 8-OH-DPAT (0.4-16nmol) in male Wistar rats impaired the acquisition of inhibitory avoidance in the elevated T-maze, increased the percentage of time spent in the lit compartment of the light-dark transition model and enhanced the number of punished drinking events in the Vogel conflict test, all changes compatible with an anxiolytic effect. This agonist also impaired escape expression in the elevated T-maze, suggestive of a panicolytic-like effect. 8-OH-DPAT-induced changes in the elevated T-maze and light-dark tests were blocked by previous local administration of the 5-HT1A-R antagonist WAY-100635 (0.37nmol) and were also observed after intra-BLA microinjection of the benzodiazepine receptor agonist midazolam (10-40nmol). Thus, stimulation of 5-HT1A-Rs in the BLA causes both anxiolytic- and panicolytic-like effects, what may have implications for the pathophysiology and treatment of generalized anxiety and panic disorders.

背景与目标： : 杏仁核 (BLA) 基底外侧核的5-HT1A和5-HT2C受体与焦虑相关的防御反应的介导之间的相关性早已得到认可。尽管有强有力的证据支持后者受体的激活引起焦虑，但据报道，前一个结合位点的作用存在矛盾。在这项研究中，我们进一步研究了5-HT1A受体 (5-HT1A-Rs) 参与焦虑和恐慌相关防御行为的调节。结果表明，在雄性Wistar大鼠中BLA内注射5-HT1A-R激动剂8-OH-DPAT (0.4-16nmol) 会损害T型迷宫中抑制性回避的获得，在Vogel冲突测试中，增加了在明暗过渡模型的照明室中花费的时间百分比，并增加了受惩罚的饮酒事件的数量，所有变化均与抗焦虑作用兼容。这种激动剂还损害了升高的T迷宫中的逃逸表达，暗示了类解毒作用。通过先前局部施用5-HT1A-R拮抗剂WAY-100635 (0.37nmol) 阻断了升高的T迷宫和明暗测试中的8-oh-dpat诱导的变化，并且在BLA内微注射苯二氮卓受体激动剂咪达唑仑 (10-40nmol) 后也观察到。因此，在BLA中刺激5-HT1A-Rs会引起抗焦虑和类抗焦虑作用，这可能对广泛性焦虑症和恐慌症的病理生理学和治疗产生影响。

BACKGROUND & AIMS: :Social hierarchy is considered to impart an adaptive advantage to the species by reducing long-term conflict between conspecifics. While social stratification is frequently established via stress-inducing stimuli, the subsequent integration of individuals into the hierarchy may attenuate anxiety. Presently, we hypothesized that repeated reinforcement of murine social hierarchy in the dominant-submissive relationship (DSR) food-competition test would engender divergent neuroplastic changes mediating both social and anxiety-like behavior among selectively-bred Dominant (Dom) and Submissive (Sub) mice. Two weeks of repeated respective social victory or defeat reduced serum corticosterone levels of both Dom and Sub mice, whereas socially-defeated Sub mice demonstrated markedly greater exploration of the open arms of the elevated plus maze (EPM). At the same time, social victory led to markedly greater expression of the immediate-early genes (IEGs) c-Jun and EGR-1 in the lateral septal nucleus (LSN) among Dom mice, in contrast with defeated Sub counterparts which demonstrated four-fold greater IEG expression in the cingulate gyrus (Cg). These findings point towards involvement of the Cg in the anxiety-like effect among Sub mice after repeated social defeat, and suggest stabilization of the social hierarchy to attenuate the stress-inducing nature of social interaction, particularly for subordinates. Further study of the potentially anxiolytic-like effects of Cg activity should shed light upon the functional significance of the Cg in social interaction, social hierarchical sorting and anxiety.

背景与目标： : 社会等级被认为是通过减少物种之间的长期冲突来赋予物种适应性优势。尽管社会分层通常是通过诱发压力的刺激来建立的，但随后将个人整合到层次结构中可能会减轻焦虑。目前，我们假设在优势-顺从关系 (DSR) 食物竞争测试中反复强化鼠的社会等级会引起不同的神经可塑性变化，从而介导选择性繁殖的优势 (Dom) 和顺从 (Sub) 小鼠的社交和焦虑样行为。反复进行两周的社交胜利或失败会降低Dom和子小鼠的血清皮质酮水平，而社交失败的子小鼠则表现出对高架迷宫 (EPM) 的张开臂的更大探索。同时，社交胜利导致Dom小鼠中外侧间隔核 (LSN) 中即刻早期基因 (IEGs) c-6月和EGR-1的表达明显增加，而被击败的亚对应物显示出四倍的IEG表达在扣带回 (Cg) 中。这些发现表明，在反复的社交失败后，Cg参与了亚小鼠的焦虑样效应，并建议稳定社会等级制度以减轻社会互动的压力诱发性质，特别是对于下属。对Cg活动潜在的抗焦虑作用的进一步研究应阐明Cg在社交互动，社会等级排序和焦虑中的功能意义。

BACKGROUND & AIMS: :Sleep is a profound regulator of cellular immunity, and the curtailment of sleep in present day lifestyle leads to disruption of neuro-immune-endocrine interactions. No therapeutic remedy is yet known for the amelioration of detrimental effects caused by sleep deprivation (SD). The current study was aimed to elucidate the effects of acute SD on immune function and its modulation by water extract from leaves of Withania somnifera (ASH-WEX). Three groups of animals, i.e. Vehicle-Undisturbed sleep (VUD), Vehicle-Sleep deprived (VSD) and ASH-WEX fed sleep deprived (WSD) rats were tested for their anxiety-like behaviour and further used for the study of inflammatory and apoptotic markers expression in piriform cortex and hippocampus regions of the brain. VSD animals showed high level of anxiety in elevated plus maze test, which was ameliorated in WSD group. The stress induced expression of inflammatory and immune response markers GFAP, TNFα, IL-6, OX-18 and OX-42 in VSD animals was found to be modulated by ASH-WEX. Further, the stress induced apoptosis was suppressed in WSD group as indicated by expression of NF-κB, AP-1, Bcl-xL and Cytochrome c. This study provides scientific validation to the anxiolytic, anti-inflammatory and anti-apoptotic properties of ASH-WEX, which may serve as an effective dietary supplement for management of SD induced stress and associated functional impairments.

背景与目标： : 睡眠是细胞免疫的深刻调节剂，当今生活方式中睡眠的减少导致神经-免疫-内分泌相互作用的破坏。尚无治疗方法可以改善由睡眠剥夺 (SD) 引起的有害影响。当前的研究旨在阐明急性SD对免疫功能的影响及其通过witsania somniifera (ASH-WEX) 叶片中的水提取物的调节作用。三组动物，即车辆-不受干扰的睡眠 (VUD)，测试了载体睡眠剥夺 (VSD) 和ASH-WEX喂养的睡眠剥夺 (WSD) 大鼠的焦虑样行为，并进一步用于研究梨状皮层和大脑海马区的炎症和凋亡标志物表达。VSD动物在升高加迷宫试验中表现出较高的焦虑水平，这在WSD组中得到改善。发现在VSD动物中，应激诱导的炎症和免疫反应标记物GFAP，tnf α，IL-6，OX-18和OX-42的表达受到ASH-WEX的调节。此外，如NF-κ b，AP-1，Bcl-xL和细胞色素c的表达所示，WSD组应激诱导的细胞凋亡受到抑制。该研究为ASH-WEX的抗焦虑，抗炎和抗凋亡特性提供了科学验证。它可以作为有效的膳食补充剂，用于管理SD引起的压力和相关的功能障碍。

BACKGROUND & AIMS: :Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage regarding their child or adult with WS. Twenty-four percent (24%) of the individuals had been prescribed an SSRI medication, while 12% had been prescribed another type of antidepressant or anxiolytic. Overall, 81% of respondents indicated that SSRI medications were either "Helpful" or "Somewhat Helpful", with paroxetine reported to be the least helpful. Sixty-four percent (64%) of survey participants reported that non-SSRI antidepressants and anxiolytics were either "Helpful" or "Somewhat Helpful" in treating symptoms of anxiety. Side effects for the antidepressants and anxiolytics were typically neurological in nature. Ten percent (10%) of the survey participants reported taking an antipsychotic medication, with risperidone and quetiapine described as more helpful than aripiprazole. Medication effectiveness may be related to the impact on serotonin levels. These findings call for further studies of medication usage in WS in order to improve their quality of life.

背景与目标： 威廉姆斯综合症 (WS) 是一种神经发育遗传病，部分以焦虑和行为困难为特征。我们研究了WS患者中抗抑郁药，抗焦虑药和抗精神病药的有效性和不良反应。共有513名父母/照顾者完成了对患有WS的儿童或成人的精神药物使用情况的调查。24% (24%) 的人被开了SSRI药物，而12% 的人被开了另一种抗抑郁药或抗焦虑药。总体而言，有81% 的受访者表示SSRI药物 “有帮助” 或 “有些帮助”，帕罗西汀被报道为最没有帮助。60 4% (64%) 的调查参与者报告说，非SSRI抗抑郁药和抗焦虑药在治疗焦虑症状方面 “有帮助” 或 “有些帮助”。抗抑郁药和抗焦虑药的副作用通常是神经性的。10% (10%) 的调查参与者报告服用抗精神病药物，利培酮和喹硫平被描述为比阿立哌唑更有用。用药效果可能与对血清素水平的影响有关。这些发现要求进一步研究WS中的药物使用情况，以改善其生活质量。

BACKGROUND & AIMS: AIM AND OBJECTIVES:To evaluate anxiolytic effect of stem bark ethanol and chloroform extracts of Erythrina mysorensis in mice. MATERIALS AND METHODS:The anxiolytic activity was examined by using the elevated plus maze (EPM) and open field test (OFT), and motor coordination by rotarod test (RRT). Twenty four Swiss albino male mice were divided into four groups of six mice each. Group 1 received vehicle (normal saline); group 2 received diazepam (1 mg/kg); groups 3 and 4 received ethanolic and chloroform extract of Erythrina mysorensis, 200 and 400 mg/kg p.o., respectively. RESULTS:Mice treated with diazepam (1 mg/kg, p.o.) showed significant (P < 0.001) increase ini the percentage of open arms entries and time spent whereas, in closed arm the number of entries and time spent were significantly (P < 0.05) decreased. Oral administration of chloroform and ethanol extract of E. mysorensis exhibited significant (P < 0.05) increase in the number of open arm entries and time spent with significant (P < 0.05) reduction in number of entries and time spent in the closed arm as compared to group 1. Chloroform and ethanol extracts treated mice also produced significant increase in the number of rearings (P < 0.05), assisted rearings and number of squares crossed (P < 0.01). Rotarod test showed significant (P < 0.01) reduction in motor activity at 45 min with diazepam and E. mysorensis extracts (400 mg/kg) as compared to groups 3 and 1. CONCLUSION:Erythrina mysorensis possess significant anxiolytic activity in the mice. It can be a promising anxiolytic agent.

背景与目标：

BACKGROUND & AIMS: :We investigated the mechanism underlying the anxiolytic actions of the neuropeptide nociceptin/orphanin FQ (N/OFQ) using the elevated plus-maze test and T-maze test. Microinfusions of N/OFQ (10 or 32pmol) into the central amygdala (ACE) increased the time spent in the open arms of the elevated plus-maze (anxiolytic-like effects), whereas microinfusions of N/OFQ (10, 32 or 100 pmol) into the basolateral amygdala (ABL) did not affect the time spent in the open arms. Moreover, microinfusions of N/OFQ (32 pmol) into the ACE impaired escape performance from the open arms of the elevated T-maze (anxiolytic-like effects), but did not change inhibitory avoidance of the open arms. A non-peptidyl N/OFQ receptor (NOP) antagonist, J-113397(1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one) (10 mg/kg, s.c.), blocked the anxiolytic-like effects induced by N/OFQ. These results indicate that the anxiolytic-like effects of N/OFQ might be due to impaired escape performance from the open arms and it implicates the N/OFQ system within the ACE in the mediation of panic action.

背景与目标： : 我们使用高架迷宫测试和T迷宫测试研究了神经肽伤害肽/孤儿院蛋白FQ (N/OFQ) 的抗焦虑作用的潜在机制。将N/OFQ (10或32pmol) 微量输注到中央杏仁核 (ACE) 中会增加在高架迷宫的张开臂中花费的时间 (类抗焦虑作用)，而N/OFQ的微量输注 (10，32或100 pmol) 进入基底外侧杏仁核 (ABL) 不影响在张开臂上花费的时间。此外，将N/OFQ (32 pmol) 微量注入ACE会损害T迷宫升高的张开臂的逃逸性能 (抗焦虑样作用)，但不会改变张开臂的抑制性避免。非肽基N/OFQ受体 (NOP) 拮抗剂，J-113397(1-[(3R，4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-乙基-1,3-二氢-2h-苯并咪唑-2-酮) (10 mg/kg，s.C.)，阻断了N/OFQ诱导的抗焦虑作用。这些结果表明，N/OFQ的抗焦虑作用可能是由于张开臂的逃逸性能受损所致，并且它暗示ACE中的N/OFQ系统参与了恐慌行动的调解。

BACKGROUND & AIMS: :Mental stress, such as anxiety and conflict, causes physiological changes such as dysregulation of autonomic nervous activity, depression, and gastric ulcers. It also induces glucocorticoid production and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels. We previously reported that Acanthopanax senticosus HARMS (ASH) exhibited anxiolytic activity. Thus, we attempted to identify the anxiolytic constituents of ASH and investigated its influence on hippocampal BDNF protein expression in male Sprague Dawley rats administered chlorogenic acid (CHA), ( +)-syringaresinol-di-O-β-D-glucoside (SYG), or a mixture of both (Mix) for 1 week using the open field test (OFT) and improved elevated beam walking (IEBW) test. As with ASH and the benzodiazepine anxiolytic cloxazolam (CLO), Mix treatment significantly increased locomotor activity in the OFT. CHA and Mix increased the time spent in the open arm in the IEBW test. SYG and Mix treatment inhibited the significant increase in normalized low-frequency power, indicative of sympathetic nervous activity, and significant decrease in normalized high-frequency power, indicative of parasympathetic nervous activity, as observed in the IEBW test. SYG and Mix treatment significantly increased hippocampal BDNF protein expression. The combination of CHA and SYG possibly induces anxiolytic behavior and modulates autonomic regulation, activates hippocampal BDNF signaling as with ASH.

背景与目标： : 精神压力，例如焦虑和冲突，会导致生理变化，例如自主神经活动失调，抑郁和胃溃疡。它还诱导糖皮质激素的产生和海马脑源性神经营养因子 (BDNF) 水平的变化。我们以前曾报道过刺五加危害 (ASH) 具有抗焦虑活性。因此，我们试图鉴定ASH的抗焦虑成分，并研究其对雄性Sprague Dawley大鼠给予绿原酸 (CHA)，( )-丁香烯醇-二-O-β-D-葡萄糖苷 (SYG) 海马BDNF蛋白表达的影响。或使用开放现场测试 (OFT) 和改进的高架光束行走 (IEBW) 测试将两者混合 (混合) 1周。与ASH和苯二氮卓抗焦虑药cloxazolam (CLO) 一样，混合处理显着提高了OFT的运动活性。CHA和Mix增加了IEBW测试中张开臂的时间。SYG和Mix处理抑制了标准化低频功率的显着增加，表明交感神经活动，以及标准化高频功率的显着减少，表明副交感神经活动，如IEBW测试中观察到的。SYG和Mix处理可显着增加海马BDNF蛋白的表达。CHA和SYG的组合可能会诱导抗焦虑行为并调节自主神经调节，像ASH一样激活海马BDNF信号。

BACKGROUND & AIMS: :Valerian is one of the most commonly used herbal remedies for the treatment of insomnia and anxiety. Valerian extracts allosterically modulate GABAA receptors, an action related to valerenic acid, which is one of the active compounds determined from pharmacological studies. Derivatives of valerenic acid, i.e. acetoxy valerenic acid or hydroxy valerenic acid, do not allosterically modulate GABAA receptors, but they bind to identical binding sites. Therefore, the question arises whether they might interfere with the effects of valerenic acid. Two valerian extracts were tested in the elevated plus maze test and the tail suspension test for anxiolytic and antidepressive activity, respectively. Reference substances were diazepam (1.0mg/kg) and imipramine (30mg/kg). The extracts were standardized to the identical total amounts of the acids (0.1; 0.5; 1.0 and 2.0mg/kg), i.e. valerenic and acetoxy valerenic acid, but the ratio between the acids was different (12:1 and 1:1.5). The extract with the ratio 12:1 prolonged the time spent on the open arm significantly when 0.5mg/kg was applied. Of the other extract, with the ratio 1:1.5, four times that amount was required (2.0mg/kg). Both of the tested extracts did not show any antidepressive effect, rather the other way around, the extract with the ratio 1:1.5 prolonged the immobility phase. However, since the core body temperature was reduced by the 1.0 and 2.0mg/kg extract dose, the prolongation may be related to the temperature phenomenon and is not indicative of a specific depressive action. In conclusion, the anxiolytic activity of the valerian extract seems rather related to valerenic acid and, moreover, standardization with respect to the total amount of valerenic acids, i.e. valerenic acid together with acetoxy valerenic acid, is misleading.

背景与目标： : 缬草是治疗失眠焦虑最常用的草药之一。缬草提取物通过变构调节GABAA受体，这是与戊酸有关的作用，它是药理学研究确定的活性化合物之一。戊酸的衍生物，即乙酰氧基戊酸或羟基戊酸，不变构调节GABAA受体，但它们与相同的结合位点结合。因此，问题是它们是否会干扰戊酸的作用。分别在高架加迷宫试验和尾部悬吊试验中测试了两种缬草提取物的抗焦虑和抗抑郁活性。参考物质是地西epa (1.0 mg/kg) 和丙咪嗪 (30 mg/kg)。将提取物标准化为相同总量的酸 (0.1; 0.5; 1.0和2.0 mg/kg)，即戊烯酸和乙酰氧基戊烯酸，但酸之间的比例不同 (12:1和1:1.5)。当施用0.5mg/kg时，比例为12:1的提取物显著延长了在张开臂上花费的时间。在比例为1:1.5的其他提取物中，所需量的四倍 (2.0 mg/kg)。两种测试的提取物均未显示出任何抗抑郁作用，相反，比率为1:1.5的提取物延长了不动相。但是，由于1.0和2.0mg/kg提取物剂量降低了核心体温，因此延长可能与温度现象有关，并且不指示特定的抑郁作用。总之，缬草提取物的抗焦虑活性似乎与戊烯酸相当相关，而且，关于戊烯酸总量 (即戊烯酸与乙酰氧基戊烯酸) 的标准化具有误导性。

BACKGROUND & AIMS: :This study investigated the effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT(1B/1D) receptor antagonist GR 127,935 with a subactive dose of citalopram [selective serotonin (5-HT) reuptake inhibitor (SSRI)] on the expression of conditioned freezing, an index of fear. In the present study, acute administration of citalopram (s.c.) reduced freezing significantly at high doses (10, 30 and 100 mg/kg), while showing no significant effect at low doses (1 and 3 mg/kg). Co-administration of WAY 100,635 (0.15 mg/kg) with citalopram (3 mg/kg) reduced freezing markedly and significantly, as compared with either drug alone. However, the addition of GR 127,935 (4 mg/kg) did not potentiate the effects of citalopram (3 mg/kg) on freezing and did not enhance the effect of WAY 100,635 (0.15 mg/kg) with citalopram (3 mg/kg). Co-administration of WAY 100,635 (0.15 mg/kg) or GR 127,935 (4 mg/kg) gave no effect on high-dose citalopram (30 mg/kg)-induced inhibition of freezing behavior. These results suggest that co-administration of WAY 100,635 (0.15 mg/kg) strengthens the anxiolytic effect of citalopram (3 mg/kg) by facilitating central 5-HT neurotransmission. Since GR 127,935 (4 mg/kg) failed to accelerate the inhibition of freezing induced by citalopram (3 mg/kg) with WAY 100,635 (0.15 mg/kg) or citalopram (3 mg/kg) alone, it is suggested that blocking 5-HT1A receptors is more effective in facilitating the anxiolytic effect of citalopram than blocking 5-HT1B/1D receptors.

背景与目标： : 本研究调查了选择性5-HT1A受体拮抗剂WAY 100,635和选择性5-HT(1B/1D) 受体拮抗剂GR 127,935与亚活性剂量西酞普兰 [选择性5-羟色胺 (5-HT) 再摄取抑制剂 (SSRI)] 共同给药对条件冷冻 (恐惧指数) 表达的影响。在本研究中，在高剂量 (10、30和100 mg/kg) 下，西酞普兰 (s.c.) 的急性给药显著降低了冷冻，而在低剂量 (1和3 mg/kg) 下没有显著效果。与单独使用任何一种药物相比，路100,635 (0.15 mg/kg) 与西酞普兰 (3 mg/kg) 的共同给药显着降低了冷冻。然而，添加GR 127,935 (4 mg/kg) 不能增强西酞普兰 (3 mg/kg) 对冷冻的作用，也不能增强西酞普兰 (3 mg/kg) 对WAY 100,635 (0.15 mg/kg) 的作用。100,635 (0.15 mg/kg) 或GR 127,935 (4 mg/kg) 的共同给药对大剂量西酞普兰 (30 mg/kg) 诱导的冷冻行为抑制没有影响。这些结果表明，联合给予WAY 100,635 (0.15 mg/kg) 通过促进中枢5-HT神经传递来增强西酞普兰 (3 mg/kg) 的抗焦虑作用。由于GR 127,935 (4 mg/kg) 未能加速西酞普兰 (3 mg/kg) 与WAY 100,635 (0.15 mg/kg) 或西酞普兰 (3 mg/kg) 单独诱导的冷冻抑制，建议阻断5-HT1A受体比阻断5-HT1B/1D受体更有效地促进西酞普兰的抗焦虑作用。

BACKGROUND & AIMS: :We studied the effect of dipeptide GB-115, a retroanalogue of cholecystokinin-4 with anxiolytic properties, on the behavior of outbred rats and BALB/c and C57Bl/6 mice induced by cholecystokinin-4 receptor agonists and yohimbine. Anxiogenic agents were shown to cause anxiety in rats and C57Bl/6 mice (with an active response to stress) in the open field test and elevated plus maze test, but did not modulate the behavior of BALB/c mice exhibiting a freezing response to emotiogenic exposure. Activation of cholecystokinin-4 type 2 receptors abolished the antianxiety effect of GB-115 in BALB/c mice. This dipeptide prevented the development of cholecystokinin-4-induced anxiety in C57Bl/6 mice and outbred rats. α(2)-Adrenoceptor antagonist yohimbine did not modulate the effects of GB-115 in BALB/c mice. GB-115 did not prevent the development of yohimbine-induced anxiety in C57Bl/6 mice. Our results confirm the data on phenotype-specific activity of GB-115. We conclude that cholecystokinin-4 and GB-115 have a common pharmacological target.

背景与目标： : 我们研究了具有抗焦虑特性的cholecystokinin-4的逆转类似物二肽GB-115对近交大鼠和cholecystokinin-4受体激动剂和育亨宾诱导的BALB/c和C57Bl/6小鼠行为的影响。在野外试验和高架迷宫试验中，已显示出抗焦虑剂可引起大鼠和C57Bl/6小鼠的焦虑 (对压力有积极反应)，但并未调节BALB/c小鼠的行为表现出对情感的冻结反应暴露。cholecystokinin-4 2型受体的激活消除了BALB/c小鼠GB-115的抗焦虑作用。这种二肽阻止了C57Bl/6小鼠和近交大鼠cholecystokinin-4-induced焦虑的发展。Α (2)-肾上腺素能受体拮抗剂育亨宾不调节BALB/c小鼠中GB-115的作用。GB-115不能阻止育亨宾诱导的C57Bl/6小鼠焦虑的发展。我们的结果证实了GB-115表型特异性活性的数据。我们得出结论，cholecystokinin-4和GB-115具有共同的药理学靶标。

BACKGROUND & AIMS: :We compared two modifications of Vogel conflict test and assessed anxyolitic activity of two drugs: diazepam (benzodiazepine anxiolitic) and tenoten (ultra-low doses of antibodies to S-100 protein) in both modifications of the test. It was found that the intensity of anxiolitic effect of the drugs depends on the conditions of Vogel test.

背景与目标： : 我们比较了Vogel冲突测试的两种修改，并评估了两种药物的焦虑活性: 地西epa (苯二氮卓抗焦虑药) 和tenoten (超低剂量的S-100蛋白抗体)。发现药物的抗焦虑作用的强度取决于Vogel测试的条件。

BACKGROUND & AIMS: :Little is known about the sites of action for the behavioral effects of chronic antidepressants. The novelty-induced hypophagia (NIH) test is one of few animal behavioral tests sensitive to acute benzodiazepines and chronic antidepressants. The goals of these experiments were to examine patterns of brain activation associated with the behavioral response to novelty and identify regions that could regulate the anxiolytic effects of acute benzodiazepine and chronic antidepressant treatments, measured using the NIH test. In the first experiment, rats were treated acutely with the anxiolytic, chlordiazepoxide (2.5 or 5 mg/kg, i.p.). In separate experiments, animals were implanted with osmotic minipumps delivering vehicle or fluoxetine (5 or 20 mg/kg per day s.c.) for 3 or 28 days. NIH was assessed by giving animals access to a familiar palatable food in a novel environment. Associated brain areas were identified using c-fos immunohistochemistry. NIH was mitigated by acute chlordiazepoxide and chronic fluoxetine. Both drugs reversed novelty-induced changes in c-fos expression in the lateral division of the posterolateral part of the bed nucleus of the stria terminalis (STLP), cingulate cortex (Cg), and dorsal field CA2 of the hippocampus (dCA2). Chronic fluoxetine additionally increased c-fos expression in the anterior nucleus accumbens (aAcb) and the piriform cortex (Pir). The effects of the drugs on c-fos expression in many regions correlated with anxiolytic efficacy. These findings identified brain regions where the effects of chronic antidepressants and benzodiazepines may converge to produce anxiolytic activity, as well as distinct sites of action for the two classes of drugs.

背景与目标： : 对慢性抗抑郁药的行为影响的作用部位知之甚少。新颖性吞咽功能减退 (NIH) 测试是少数对急性苯二氮卓类药物和慢性抗抑郁药敏感的动物行为测试之一。这些实验的目的是检查与对新颖性的行为反应相关的大脑激活模式，并确定可以调节急性苯二氮卓类药物和慢性抗抑郁药治疗的抗焦虑作用的区域，使用NIH测试进行测量。在第一个实验中，用抗焦虑药氯二氮卓 (2.5或5 mg/kg，i.p.) 对大鼠进行急性治疗。在单独的实验中，将动物植入输送媒介物或氟西汀 (每天5或20 mg/kg/天s.C.) 的渗透微型ipumps，持续3或28天。通过在新颖的环境中让动物获得熟悉的可口食物来评估NIH。使用c-fos免疫组织化学鉴定相关的大脑区域。急性氯二氮卓和慢性氟西汀减轻了NIH。两种药物都逆转了新颖性诱导的c-fos表达的变化。纹状体的床核后外侧部分 (STLP)，扣带回皮层 (Cg) 和海马背场CA2 (dCA2)。慢性氟西汀还增加了伏隔核 (aAcb) 和梨状皮质 (Pir) 中c-fos的表达。药物在许多区域对c-fos表达的影响与抗焦虑功效有关。这些发现确定了慢性抗抑郁药和苯二氮卓类药物的作用可能会聚以产生抗焦虑活性的大脑区域，以及两类药物的不同作用部位。

BACKGROUND & AIMS: :Melatonin (MLT) is a neurohormone known to be involved in the regulation of anxiety. Most of the physiological actions of MLT in the brain are mediated by two high-affinity G-protein-coupled receptors, denoted MT(1) and MT(2). However, the particular role of these receptors in anxiety remains to be defined. Here we used a novel MT(2)-selective partial agonist, UCM765 to evaluate the involvement of MT(2) receptors in anxiety. Adult male rats were acutely injected with UCM765 (5-10-20mg/kg), MLT (20mg/kg) or diazepam (DZ, 1mg/kg). Anxiety-related behaviors were assessed in the elevated plus maze test (EPMT), novelty suppressed feeding test (NSFT) and open field test (OFT). UCM765 at the dose of 10mg/kg showed anxiolytic-like properties by increasing the time spent in the open arm of the EPMT, and by reducing the latency to eat in a novel environment in the NSFT. In the EPMT, animals treated with UCM765 (10mg/kg) or MLT (20mg/kg) spent more time in the open arms compared to vehicle-treated animals, but to a lesser extent compared to DZ (1mg/kg). In the NSFT, all treatments similarly decreased the latency to eat in a novel environment compared to vehicle. UCM765 and MLT did not affect the total time and the number of entries into the central area of the OFT, but unlike DZ, did not impair locomotion. The anxiolytic effects of UCM765 and MLT in the EPMT and the NSFT were blocked using a pre-treatment with the MT(1)/MT(2) antagonist luzindole (10mg/kg) or the MT(2) antagonist 4P-PDOT (10mg/kg). These results demonstrated, for the first time, the anxiolytic properties of UCM765 and suggest that MT(2)-receptors may be considered a novel target for the development of anxiolytic drugs.

背景与目标： 褪黑素 (MLT) 是一种神经激素，已知参与焦虑的调节。大脑中MLT的大多数生理作用是由两个高亲和力的g蛋白偶联受体介导的，分别表示为MT(1) 和MT(2)。然而，这些受体在焦虑中的特殊作用仍有待确定。在这里，我们使用了一种新型的MT(2) 选择性部分激动剂UCM765来评估MT(2) 受体在焦虑中的参与。成年雄性大鼠急性注射UCM765 (5-10-20 mg/kg)，MLT (20 mg/kg) 或地西epa (DZ，1 mg/kg)。在高架迷宫测试 (EPMT)，新颖性抑制喂养测试 (NSFT) 和野外测试 (OFT) 中评估了与焦虑相关的行为。10mg/kg剂量的UCM765通过增加在EPMT的张开臂中花费的时间并减少在NSFT的新环境中进食的潜伏期，显示出类似抗焦虑的特性。在EPMT中，与媒介物处理的动物相比，用UCM765 (10 mg/kg) 或MLT (20 mg/kg) 处理的动物在张开的手臂上花费的时间更多，但与DZ (1 mg/kg) 相比，其程度较小。在NSFT中，与车辆相比，所有治疗方法都类似地降低了在新环境中进食的潜伏期。UCM765和MLT不会影响进入OFT中心区域的总时间和数量，但是与DZ不同，它不会损害运动。使用MT(1)/MT(2) 拮抗剂luzindole (10 mg/kg) 或MT(2) 拮抗剂4P-PDOT预处理来阻断UCM765和MLT在EPMT和NSFT中的抗焦虑作用 (10 mg/kg)。这些结果首次证明了UCM765的抗焦虑特性，并表明MT(2) 受体可能被认为是开发抗焦虑药物的新靶标。