Comprehensive Assessment of Anxiolytic Properties in 4-HPAA Derivatives: Bridging in Vivo Validation and Molecular Docking Analyses

Anxiety is a significant mental health issue that substantially affects an individual’s quality of life. Feelings of uneasiness, irritability, and sleep disturbances characterize it. 4-Hydroxyphenyl acetic acid (4-HPAA) is identified in brain cells as a physiological byproduct of tyramine. This study hypothesizes that 4-HPAA may regulate anxiety due to its anxiolytic properties, acting as a modulator of the GABAergic system, which plays a crucial role in the pathophysiology of anxiety disorders. Our study aims to enhance the anxiolytic effects of 4-HPAA through chemical modification to improve its pharmacokinetic properties. Three derivatives, namely Isopropyl-4-hydroxy-[phenyl] acetate (IHPA), Isopropyl-4-hydroxy-[phenyl] acetate (MPAA), and 4-methoxyphenyl acetate (MPHA), have been synthesized from 4-HPAA. This assessment will use well-established animal models, specifically the Elevated Plus-Maze (EPM) and Zero Maze (EZM) tests, selected for their validity in replicating anxiety-like symptoms in animals. Chronic caffeine administration via drinking water (0.3 g/l for 14 days) was employed to induce an anxiety state for testing purposes. IHPA and MPAA demonstrated significant anxiolyticactivity when tested in the EPM and EZM experiments. Molecular docking simulations using AutoDock Vina indicated that 4-HPAA derivatives had docking scores ranging from −5.8 to −4.8 kcal/mol, compared to the standard anxiolytic medication Diazepam, which scored −7.1 kcal/mol. These scores suggest a potential for 4-HPAA derivatives to interact effectively with the Gamma-aminobutyric acid (GABA_A) receptor. In conclusion, our in vivo and in silico analyses indicate a promising anxiolytic potential for 4-HPAA derivatives.

焦虑模型大鼠下丘脑-垂体-肾上腺轴高反应性与糖皮质激素受体蛋白表达降低相关

目的研究焦虑模型大鼠在应激条件时下丘脑-垂体-肾上腺(hypothalamus-pituitaryadrenal,HPA)轴呈高反应性是与轴本身功能亢进还是与反馈调节中糖皮质激素受体(glucocorticoid steroid receptor,GR)蛋白表达改变相关。方法 SD健康雄性大鼠随机分为对照组(n=20)和焦虑模型组(n=26)。对照组正常饲养。采用不可预知的情绪应激方法建立大鼠焦虑模型。所有大鼠每周称量体质量。造模结束后,通过行为学鉴定造模是否成功。旷场和高架作为应激源刺激大鼠,测定两组大鼠血清中促肾上腺激素和皮质酮水平。Western blot检测GR蛋白在大鼠海马、下丘脑、垂体和肾上腺组织中的表达。结果焦虑模型大鼠体质量增长率与对照组相比明显降低(P<0.01)。高架十字迷宫实验和旷场实验显示:与对照组相比,模型组大鼠进入开臂次数、开臂停留时间、进入开臂次数百分比和进入开臂时间百分比均显著降低(P<0.01);总路程、中央活动路程百分比和中央活动时间百分比均显著降低(P<0.05,P<0.01)。在基础条件下,两组大鼠分泌促肾上腺激素和皮质酮差异无统计学意义(P>0.05);而应激条件下,模型组大鼠分泌两种激素显著高于对照组(P<0.01)。与对照组比较,模型组在大鼠海马、下丘脑和肾上腺组织中GR蛋白表达显著降低(P<0.05,P<0.01),而在垂体中表达差异无统计学意义(P>0.05)。结论焦虑模型大鼠在应激条件下,HPA轴反应性增加与GR所介导的负反馈调节作用减弱有关。

Anxiolytic property of hydro-alcohol extract of Lactuca sativa and its effect on behavioral activities of mice

Lactuca sativa, belonging to the Asteraceae family, is a leafy vegetable known for its medicinal properties. This study aimed to understand the mechanism of Lactuca sativa extract with respect to pharmacological action. We investigated the anxiolytic effects of hydro-alcoholic extract of leaves of Lactuca sativa on mice. The behav- ioral tests performed on mice models to assess anti-anxiety properties were： open field test （OFT）, elevated plus maze test （EPM）, elevated T maze test, and marble burying test. Increased locomotor activity and time spent in the ＂open-ann＂ were observed in extract fed group. Malondialdehyde （MDA） and nitrite levels were decreased, cata- lase and glutathione levels were increased in Lactuca sativa treated mice. The data obtained in the present study suggests that the extract of Lactuca sativa can afford significant protection against anxiolytic activity.

Neuronal protein-tyrosine phosphatase 1B hinders sensory-motor functional recovery and causes affective disorders in two different focal ischemic stroke models

Ischemic brain injury causes neuronal death and inflammation.Inflammation activates protein-tyrosine phosphatase 1B(PTP1B).Here,we tested the significance of PTP1B activation in glutamatergic projection neurons on functional recovery in two models of stroke:by photothrombosis,focal ischemic lesions were induced in the sensorimotor cortex(SM stroke)or in the peri-prefrontal cortex(peri-PFC stroke).Elevated PTP1B expression was detected at 4 days and up to 6 weeks after stroke.While ablation of PTP1B in neurons of neuronal knockout(NKO)mice had no effect on the volume or resorption of ischemic lesions,markedly different effects on functional recovery were observed.SM stroke caused severe sensory and motor deficits(adhesive removal test)in wild type and NKO mice at 4 days,but NKO mice showed drastically improved sensory and motor functional recovery at 8 days.In addition,peri-PFC stroke caused anxiety-like behaviors(elevated plus maze and open field tests),and depression-like behaviors(forced swimming and tail suspension tests)in wild type mice 9 and 28 days after stroke,respectively,with minimal effect on sensory and motor function.Peri-PFC stroke-induced affective disorders were associated with fewer active(FosB+)neurons in the PFC and nucleus accumbens but more FosB+neurons in the basolateral amygdala,compared to sham-operated mice.In contrast,mice with neuronal ablation of PTP1B were protected from anxiety-like and depression-like behaviors and showed no change in FosB+neurons after peri-PFC stroke.Taken together,our study identifies neuronal PTP1B as a key component that hinders sensory and motor functional recovery and also contributes to the development of anxiety-like and depression-like behaviors after stroke.Thus,PTP1B may represent a novel therapeutic target to improve stroke recovery.All procedures for animal use were approved by the Animal Care and Use Committee of the University of Ottawa Animal Care and Veterinary Service(protocol 1806)on July 27,2018.

Predator stress-induced depression is associated with inhibition of hippocampal neurogenesis in adult male mice

Stress has been suggested to disturb the 5-hydroxytryptamine system and decrease neurogenesis, which contribute to the development of depression. Few studies have investigated the effect of predator stress, a type of psychological stress, on depression and hippocampal neurogenesis in adult mice; we therefore investigated this in the present study. A total of 35 adult male Kunming mice were allocated to a cat stress group, cat odor stress group, cat stress + fluoxetine group, cat odor stress + fluoxetine group, or a control group(no stress/treatment). After 12 days of cat stress or cat odor stress, behavioral correlates of depression were measured using the open field test, elevated plus maze test, and dark-avoidance test. The concentrations of hippocampal 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were measured using high-performance liquid chromatography-electrochemical detection. Neurogenesis was also analyzed using a bromodeoxyuridine and doublecortin double-immunostaining method. Cat stress and cat odor stress induced depression-like behaviors; this effect was stronger in the cat stress model. Furthermore, compared with the control group, cat stress mice exhibited lower 5-hydroxytryptamine concentrations, higher 5-hydroxyindoleacetic acid concentrations, and significantly fewer bromodeoxyuridine+/doublecortin+-labeled cells in the dentate gyrus, which was indicative of less neurogenesis. The changes observed in the cat stress group were not seen in the cat stress + fluoxetine group, which suggests that the effects of predator stress on depression and neurogenesis were reversed by fluoxetine. Taken together, our results indicate that depression-like behaviors induced by predator stress are associated with the inhibition of hippocampal neurogenesis.

Effects of clonidine on anxiety-like behaviors of rats subjected to chronic hypoperfusional cerebral ischemia

Aim To investigate the effect of clonidine on anxiety-like behaviors of rats subjected to chronic hy- popeffusional cerebral ischemia. Methods Chronic hypopeffusional cerebral ischemia was established by perma- nent bilateral common carotid arteries occlusion （two-vessel occlusion, 2VO）. Three weeks after 2VO, rats were given clonidine （0.05 mg·kg^-1, i. p. ） for 14 days. Behavioural experiments including elevated plus maze （EPM） and open field test （OFT） were applied to evaluate anxiey-like behaviour after four-week ischemia. Re- suits 2VO rats significantly spent less time in open arm of EPM and more time in peripheral region of OFT com- pared with sham rats. Clonidine notably increased open arm time in EPM and prolonged time spent in center region in OFT of 2VO rats. Conlusion Chronic hypopeffusional cerebral ischemia caused anxiety-like behaviors of rats and clonidine showed an important role in improving anxiety-like behaviors in 2VO rats.

Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission

Recent studies have shown the importance of the GABA-ergic transmission in the pathophysiology of anxiety and depressive disorders in humans. Our present study aims to investigate the interaction of melatonin (MEL) with this system by exploring the effects of MEL with or without a facilitator of GABA-ergic neurotransmission, diazepam (DZ) on the levels of depression and anxiety in Wistar rats. For this purpose, different doses of MEL (2, 4 or 16 mg/kg) or DZ (2 mg/kg) are subchronically administered during 15 days. After pharmacological treatments, anxiety levels are evaluated in behavioral tests of Open Field (OFT) and elevated plus maze (EPM) and depression levels are evaluated by the forced swim test (FST). The results showed that MEL produces anxiolytic-like and antidepressant-like effects in a dose-dependent manner;the maximum effect was obtained at a dose of 16 mg/kg. However, a dose of 4 mg/kg is necessary to induce an effect. The effect of MEL and DZ reported in this study concerns selective modulation of behavioral anxiety and depression since locomotor activity assessed by the OFT and EPM was not affected. The subchronic injection of MEL at 4 mg/kg, DZ at 2 mg/kg or the two combined molecules also induces also anxiety-like and antidepressant-like behavior. In addition, a potentiating effect between MEL and DZ was observed. These effects suggest that psychopharmacological actions of MEL are due, at least in part, to its ability to improve the central GABA-ergic transmission.

Modulation of Anxiolytic-Like and Antidepressant-Like Effects of Melatonin by Imipramine in Wistar Rats: Possible Interaction with Central Monoaminergic Systems

Our current study aims to explore the interaction of melatonin (MEL) with the monoaminergic system on the pathophysiology of affective disorders in Wistar rats. We mention here that, the role of monoaminergic transmission in the pathophysiology of affective disorders in humans is demonstrated in most recent reports. In this sense, our current work aims to explore the effect of melatonin (MEL) with or without imipramine (IMP) on levels of depression and anxiety in Wistar rats and would determine the role of MEL in modulating serotonin, noradrenaline and dopamine neurotransmission. From this point, twenty-four female Wister rats were divided into 4 groups of 6 animals and received subcutaneously during 4 weeks different doses of MEL (4 mg/kg), IMP (2 mg/kg) or MEL (4 mg/kg) + IMP (2 mg/kg). Behavioral performance especially anxiety and depression is measured in the open field (OFT), elevated plus maze (EPM) and forced swim test (FST). The anxiety-like and antidepressant-like effects were observed with MEL at 4 mg/Kg and IMP at 2 mg/Kg but the potentiating effect was more observed with the two combined molecules (MEL and IMP), since locomotors activity assessed by the OFT and EPM was not affected. These effects suggest that psychopharmacological actions of MEL are due, at least in part, to its ability to potentiate the central monoaminergic transmitter effects.

Behavioral Characteristics of Pharmacologically Selected Lines of Rats: Relevance to Depression

This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential hypothermic and behavioral responses to the anticholinesterase, diisopropylfluorophosphate (DFP). FSL rats are more sensitive to the hypothermic effects of cholinergic, serotonergic, and dopaminergic agonists but less sensitive to the locomotor or stereotypic effects of dopamine agonists. FSL rats exhibit greater immobility in the forced swim test and reduced social interaction compared with FRL rats, but do not differ in saccharin intake, behavior in the elevated plus maze, or responses for rewarding brain self-stimulation. The exaggerated immobility and reduced social interaction are counteracted by chronic treatment with antidepressants. Because FSL rats were more sensitive to 5-HT1A receptor agonists, high (HDS) and low (LDS) 8-OH-DPATsensitive lines were selectively bred for differential hypothermic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). HDS rats were also more sensitive to the hypothermic effects of oxotremorine, a cholinergic agonist, but selection for this response did not diverge with later selection. HDS rats exhibited greater immobility in the forced swim test than LDS rats and this correlated response could be seen early in selection (generation 3). HDS rats also showed reduced social interaction compared to LDS rats, but did not differ in behavior in the elevated plus maze. These findings confirm that selection for hypothermic responses to pharmacological agents do have behavioral consequences, notably the production of depressive-like phenotypes, which can be counteracted by chronic antidepressant treatment. Because increased 5-HT1A receptor sensitivity was common to both selected lines (FSL and HDS), neurobiological processes dependent on this receptor could contribute to the abnormal behaviors that manifest in these rat lines and thus suggesting a mechanism underlying depressive behaviors in humans. However, available human data are inconsistent with this hypothesis and suggest that other mechanisms underlie these behavioral abnormalities in HDS and FSL rats. These mechanisms as well as additional behavioral testing in these rat lines will be discussed.

焦虑大鼠模型高架十字迷宫实验的复测信度检验及参数相关性分析

目的:探讨高架十字迷宫(elevated plus-maze,EPM)作为焦虑大鼠模型评价方法的复测信度及其参数相关性。方法:将成年雌性Wistar大鼠放入高架十字迷宫中,摄像系统记录5 min的行为变化,实验间隔1周进行2次;实验参数如下:进入开放臂次数、进入封闭臂次数、向下探究次数、封闭臂后腿直立次数、进入开放臂时间、进入封闭臂时间。结果:①组内相关系数(ICC)结果表明,除封闭臂后腿直立次数和向下探究次数初测与复测相关性差外,其他参数均显示EPM的初测与复测具有较好的相关性。②一致性系数(Kappa)结果表明,所有参数均显示EPM复测可信度较好,Kappa值均>0.5。结论:进入开放壁时间百分比、进入开放壁次数百分比和总进臂次数在EPM初测及复测实验中均呈较好复测信度。

中国林蛙卵油的抗焦虑作用

目的研究中国林蛙卵油 (eggoilofRanatemporariachensinensisDavid ,EORTCD)的抗焦虑作用。方法应用高架十字迷路和小鼠爬梯实验评价中国林蛙卵油的抗焦虑活性及其量效、时效关系。结果与对照组比较 ,EORTCD 2 0、4 0 g·kg-1能显著延长大鼠在十字迷路开放通路连续停留时间 ,增加大鼠进入开放通路次数 ,而对封闭通路连续停留时间和进入封闭通路次数无明显影响 ;小鼠爬梯实验中 ,EORTCD 1 4～5 6g·kg-1组小鼠站立数明显减少而爬梯数无显著差异 ;EORTCD抗焦虑时效实验表明在给药后 3 0、60min抗焦虑活性较强 ;γ 氨基丁酸 (γ aminobutyricacid ,GABA) 5 0、1 0 0mg·kg-1分别与EORTCD 1 2 g·kg-1联合给药组的小鼠站立数显著降低而爬梯数无显著减少 ,且比单独给予EORTCD组小鼠站立数少。结论中国林蛙卵油有明显抗焦虑作用。

谷维素和维生素B_1增强地西泮的抗焦虑作用

目的 :研究地西泮、谷维素和维生素B1按 1∶32∶8的比例合用后的抗焦虑作用 ,并同地西泮比较。方法 :采用大、小鼠高架十字谜宫模型和大鼠五甲烯四氮唑辨别效应对抗模型。结果 :在大、小鼠高架十字迷宫实验中 ,地西泮与谷维素和维生素B1合用后 ,大、小鼠在开放臂停留时间百分率明显增加 ,表现出明显的抗焦虑作用 ;而且其在开放臂停留时间百分率的增加 ,明显高于单独使用与其含量相等的地西泮的作用。在大鼠五甲烯四氮唑辨别效应对抗实验中 ,合用后对抗大鼠五甲烯四氮唑辨别效应的ED50 值为 2 3.4mg·kg-1,其地西泮含量为 0 .6mg·kg-1,远低于地西泮单方的ED50 值 3.5mg·kg-1。结论

痛抑郁二联征模型大鼠中缝背核不同水平5羟色胺表达差异

目的探讨痛抑郁二联征模型大鼠中缝背核(DRN)5羟色胺(5-HT)阳性细胞的分布特点。方法20只雄性SD大鼠随机分为对照组和模型组。模型组大鼠连续3d皮下注射利血平,每日1次,以诱发痛抑郁二联征模型。模型制作后第1天和第2天检测左后足机械缩足阈观察大鼠痛阈变化,模型制作后第2天旷场实验和高架O迷宫实验检测大鼠情绪变化,免疫荧光技术观察DRN前囟后6.8mm、7.3mm和7.8mm水平的5-HT表达。结果模型组大鼠经利血平注射后机械痛阈显著下降,并产生抑郁样行为。对照组的DRN前囟后6.8mm、7.3mm和7.8mm水平的5-HT阳性细胞表达量分别为106.00±10.21、96.67±24.50和195.67±2.33。模型组相应的表达量分别为61.67±14.53,72.33±34.35和53.67±26.77。除前囟后7.8mm水平模型组与对照组相比有显著性差异(P<0.05)之外,其他两个水平5-HT阳性细胞表达量模型组和对照组之间差异无显著性(P>0.05)。结论利血平诱导的痛抑郁二联征大鼠模型以及中缝背核5-HT表达的降低,可能主要与DRN前囟后7.8mm水平的5-HT阳性细胞数变化有关,而与前囟后6.8mm和后7.3mm水平无关。

钩吻素子对大鼠焦虑行为的影响

目的进一步明确钩吻素子是否具有抗焦虑作用。方法以大鼠高架十字迷宫实验为动物模型,评价钩吻素子单次皮下注射给药和连续皮下注射给药的抗焦虑活性及特点。结果钩吻素子能显著增加大鼠进入高架十字迷宫开臂次数和在开臂的停留时间百分率(P<0.05,P<0.01);钩吻素子在实验剂量下对大鼠自主运动活性无影响(P>0.05)。结论钩吻素子可能具有抗焦虑作用。

钩吻素子对孤立大鼠的抗焦虑作用及其机制

目的研究钩吻素子连续皮下给药对孤立大鼠抗焦虑样行为的影响,并探讨其作用机制。方法 Wistar大鼠单笼饲养18 d,第12天开始每天皮下注射钩吻素子0.5、1.5 mg/kg 1次,连续给药7 d。孤立饲养第17天(即给药第6天)进行高架十字迷宫试验,试验最后1 d(即给药第7天)进行自主活动试验和群居接触试验。行为学试验结束后,通过酶联免疫吸附测定(ELISA)检测动物血浆中促肾上腺皮质激素(ACTH)和皮质酮浓度,并测定海马中孕酮和别孕烯醇酮的含量。结果钩吻素子连续给药6 d能有效提高孤立大鼠在高架十字迷宫开臂区的活动情况,提示钩吻素子具有抗焦虑作用;钩吻素子连续给药7 d对大鼠自主活动无影响,但能提高配对孤立大鼠的接触次数和接触时间,进一步证明了钩吻素子的抗焦虑效应。与模型组比较,钩吻素子1.5 mg/kg治疗组能降低孤立大鼠血浆中的皮质酮水平(P<0.05),钩吻素子0.5、1.5 mg/kg治疗组均能提高大鼠海马中的别孕烯醇酮含量(P<0.01);而各组动物血浆中的ACTH浓度和海马中的孕酮含量则未见变化。结论钩吻素子连续给药能增加孤立大鼠的抗焦虑样行为,其抗焦虑作用可能与调节大鼠海马的别孕烯醇酮含量和抑制下丘脑-垂体-肾上腺轴异常活动有关。

生命早期孤养对小鼠应激易感性的影响

目的:观察生命早期母婴分离对小鼠应激易感性及认知能力的影响。方法:新生的小鼠于出生后第2天随机分为正常饲养组(N组:正常饲养,n=9)、长时间母婴分离组(LMS组:分离3 h,n=9)及短时间母婴分离组(BMS组:分离15 min,n=8)。3组小鼠出生后21 d断乳,断乳后常规饲养。小鼠成年后,用幽闭+电击的方法对3组小鼠给予急性应激,应激之后借助旷场实验、高架十字迷宫、水迷宫实验评价小鼠的情绪及学习记忆能力。结果:在旷场实验中,与N组比较,LMS及BMS组小鼠的外周路程明显增加,差异具有统计学意义(P<0.05);在高架十字迷宫中,LMS组较N组进入闭臂次数明显增多,差异具有统计学意义(P<0.05),BMS组与N组比较差异不具有统计学意义;在水迷宫实验中LMS组与BMS组小鼠的成绩与N组比较差异均无统计学意义。结论:①生命早期长时间母婴分离可以增强小鼠应激易感性,而短时间母婴分离影响不显著;②生命早期母婴分离对应激后小鼠的认知能力影响不明显。

大脑中动脉线栓法复制卒中后创伤后应激障碍样大鼠模型的建立

目的探索用大脑中动脉线栓法(MCAO)建立卒中后创伤后应激障碍(PTSD)样大鼠模型的可行性。方法将45只大鼠随机分为模型对照组、假手术组、单次延长应激(SPS)组。对模型对照组和假手术组采用MCAO造模,对SPS组采用SPS造模,造模后7,14d采用高架十字迷宫和社交趋避实验观察不同处理组大鼠的行为改变情况。14d后检测大鼠海马内GAD67、GAD65和GLT1的基因表达情况。结果社交趋避实验中,与假手术组比较,模型对照组与SPS组在两个时间点的潜伏期延长(P<0.05,P<0.01)、社交区进入时间明显缩短(P<0.01),在14d时社交区进入次数、直立次数均明显减少(P<0.01);高架十字迷宫实验中,与假手术组比较,14d时模型对照组与SPS组开放壁进入时间比和进入次数比均减少(P<0.05)。在两个实验的两个时间点,模型对照组与SPS组大鼠行为学均未出现明显差异(除站立次数外)。PCR检测显示,与假手术组比较,模型对照组和SPS组大鼠海马内GAD67、GAD65和GLT1的基因表达均减少(P<0.05,P<0.01),SPS组的GAD67表达差异无统计学意义。结论MCAO造模方法使大鼠出现了一定程度的PTSD状态。

一种新的大鼠创伤后应激障碍模型的建立及其行为学检测

目的采用复合应激刺激探索建立一种新的创伤后应激障碍(posttraumatic stress disorder,PTSD)大鼠模型,观察其行为学变化。方法 30只成年SD大鼠,随机分为正常对照组、连续单一应激组(single-prolonged stress,SPS)和复合应激组,每组10只。用束缚、电击、力竭游泳复合应激源建立大鼠模型,14 d后利用迷宫、旷场实验检测其行为学变化,评估模型效果。结果在接受复合应激后第14天大体行为学观察、拒俘反射评分、旷场试验、高架十字迷宫以及水迷宫结果表明复合应激组大鼠较正常对照组及SPS组,显示出显著的PTSD样症状行为学改变,活动性降低、焦虑样行为增多、空间记忆能力受损。①复合应激组拒俘反射评分(1.4±1.0)较SPS组及正常对照组显著增加(P<0.05,P<0.01)。②旷场实验:复合应激组跨格次数(27.80±5.55)和站立次数(9.00±2.49)较SPS组及正常对照组显著减少(P<0.05,P<0.01);修饰次数无显著差异。③高架十字迷宫实验:复合应激组进入开放臂次数比例(27.50±1.35)、进入开放臂时间比例(29.62±3.23)以及OE+CE(8.60±3.63)较SPS组及正常对照组显著降低(P<0.05,P<0.01);向下探究次数和站立次数均无显著差异。④水迷宫实验的第1、2天3者无显著差异,第3天和第4天复合应激组(35.67±5.13、25.09±3.55)较SPS组及正常对照组时间显著延长(P<0.05,P<0.01)。水迷宫空间探索实验中,复合应激组进入目标象限次数(5.80±2.34)以及穿越原平台位置次数(3.10±1.79)较SPS组及正常对照组显著减少(P<0.05,P<0.01)。结论通过大鼠行为学检测证实复合应激刺激可成功制备较典型的大鼠PTSD动物模型。

大鼠吗啡依赖戒断后焦虑模型的建立和评价

目的:利用高架十字迷宫建立大鼠吗啡戒断后焦虑模型。方法:342只大鼠按给药总时间的不同,随机分为7、10、14d3大组。每大组各114只,按戒断时间的不同再分设戒断0、24、48、72、96、120、144h、丁螺环酮治疗、生理盐水对照共9小组。采用剂量递增法给药,建立吗啡依赖模型后自然戒断,用高架十字迷宫观察各组大鼠焦虑行为。结果:(1)7d大组,戒断后48h表现出焦虑症状,与生理盐水组比较,其OE、OT、OE%、OT%4项指标均下降(P<0.05)。(2)10d大组,与生理盐水组比较,戒断后48、72、96h均表现出焦虑症状(P<0.05),其中又以72h组最为显著,OE、OT、OE%均明显下降(P<0.01);丁螺环酮治疗组与戒断72h组比较,其OE、OT、OT%均增高(P<0.05),OE%显著增高(P<0.01)。(3)14d给药组,与10d给药组相类似,典型的焦虑症状也出现在戒断后72h,与生理盐水组比较,OE、OT、OT%均明显降低(P<0.01),OE%降低(P<0.05);丁螺环酮组与戒断72h组比较,OE%、OT、OT%均明显增高(P<0.01),OE增高(P<0.05)。结论:吗啡持续给药7、10、14d大鼠通过自然戒断均能成功建立吗啡戒断后焦虑模型,但以10d、戒断72h为最佳。该模型可较为客观和准确地反映吗啡依赖戒断后焦虑行为。

紫果西番莲叶抗焦虑药效研究

目的:考察紫果西番莲叶醇提物及其3个分离部位即乙酸乙酯部位、水饱和正丁醇部位及其水部位的抗焦虑作用。方法:采用国际通用的高架十字迷宫焦虑动物模型,观察紫果西番莲叶醇提物及其分离部位对小鼠的行为的影响。结果:紫果西番莲叶醇提物在400 mg/kg,800 mg/kg时表现出了比较明显的抗焦虑作用,同时乙酸乙酯部位、水饱和正丁醇部位以及水部位在100 mg/kg,200 mg/kg,300 mg/kg时也都表现出了比较明显的抗焦虑作用。