目的 基于"趋避冲突理论(the approach-avoid-ance conflict theory)"设计和发明梁氏情境应激箱(Liang's contextual-stress box,Liang's box),旨在诱导小鼠焦虑样行为.该研究主要目的在于,与经典焦虑相关动物行为学测试模型高架十字迷宫(elevated plus maze,EPM)和旷场(open field,OF)相比较,阐明和分析Liang's box优缺点,初步评价其预测效度.方法 Liang's box由1个开放的圆形中央区和3个封闭的长方形外周臂组成.将小鼠分别放入Liang's box、EPM和OF中,令其自由探索15 min,记录、分析和比较3种实验方法的时空数据和行为学指标.小鼠ip给予地西泮(0.5,1.0和2.0 mg·kg-1)和丁螺环酮(0.5,2.0和10 mg·kg-1),研究药物对Liang's box诱导小鼠特征性行为的影响.结果 ①与EPM和OF相比,Liang's box在具有同样简便操作的同时,还具有结构冲突应激强度适中、模型探索面积恰当、区域定义及划分明确、输出数据离散程度小的优势;② Liang's box时空数据涉及7个方面,分别为潜伏期、停留时间、活动路程、运动速度、活动度、不动时间和区间探索.相比之下,时空数据对小鼠行为的评估更加全面;③与EPM和OF相比,Liang's box可以诱导小鼠更多的特征性行为表现,如更多的探索活动、发生更多风险评估行为,并诱发了独特的"家基现象";④因子分析解析了Liang's box诱导小鼠焦虑样状态的7个方面,其中包括一般焦虑、风险评估、向外探索、垂直探索、一般活动、警惕性和家基行为;⑤ 初步评价实验表明:地西泮和丁螺环酮对Liang's box诱导小鼠的特征性行为具有明确的干预作用.结论 作为新型焦虑相关小鼠行为学测试模型,Liang's box在本研究中展现了其在情境应激结构、小鼠行为诱导方面的优势和潜力,并在预测效度评价中具有良好的表现,有望从行为药理学角度为焦虑机制研究和抗焦虑药物筛选工作提供新的方向.

AimsOpioid addiction is a major public health issue, yet its underlying mechanism is still unknown. The aim of this study was to explore the roles of ubiquitin-proteasome system (UPS) and regulator of G protein signaling 4 (RGS4) in morphine-induced behavioral sensitization, a well-recognized animal model of opioid addiction. MethodsWe explored the characteristics of RGS4 protein expression and polyubiquitination in the development of behavioral sensitization induced by a single morphine exposure in rats, and the effect of a selective proteasome inhibitor, lactacystin (LAC), on behavioral sensitization. ResultsPolyubiquitination expression was increased in time-dependent and dose-related fashions during the development of behavioral sensitization, while RGS4 protein expression was not significantly changed during this phase. Stereotaxic administration of LAC into nucleus accumbens (NAc) core inhibited the establishment of behavioral sensitization. ConclusionUPS in NAc core is positively involved in behavioral sensitization induced by a single morphine exposure in rats. Polyubiquitination was observed during the development phase of behavioral sensitization, while RGS4 protein expression was not significantly changed, indicating that other members of RGS family might be substrate proteins in UPS-mediated behavioral sensitization.

Accepted abstracts under the theme: Electronic Poster (n=8)

焦虑障碍是当下比较普遍的精神类疾病,其发病机制除了受遗传因素的影响之外,表观遗传学修饰同样发挥了非常关键的调控作用.DNA甲基化是表观遗传修饰的一种重要形式,具有很强的环境敏感性,许多基因在环境应激下的甲基化改变可对焦虑障碍等精神类疾病产生影响.本文主要阐述了糖皮质激素受体基因(NR3C1)、脑源性神经营养因子(BDNF)基因、催产素受体(OX-TR)基因以及神经肽Y(NPY)基因等应激相关基因的甲基化修饰与焦虑障碍之间的密切关联.

目的 建立大鼠和小鼠脑电图头部皮下电极埋置新方法,并检验脑电信号采集的可行性和有效性.方法 采用自行设计改造的颅内电极"头皮包埋式"埋置法,安装大鼠和小鼠头部脑电电极,并考察脑电电极装置的稳定性.用MP150多导生理信号记录仪和脑电数据分析软件SleepSign(版本:3.2.6.1404)采集和分析大鼠和小鼠的脑电信号,比较传统裸露式电极安装法和"头皮包埋式"埋置法采集脑电信号的一致性.用"头皮包埋式"埋置法,采集和比较大鼠和小鼠麻醉和清醒状态时脑电信号特征,观察不同周龄(8,10和12周)对大鼠脑电频率和相对功率的影响.结果 在实验周期内,用传统裸露式电极安装法,大鼠和小鼠头部脑电图装置分别脱落3/10和2/10;"头皮包埋式"埋置法埋置的大鼠和小鼠头部脑电图装置未见脱落,术后切口愈合良好,进食进水及一般行为活动未受明显影响,且该法与传统方法所采集的脑电图相对功率在各频段的分布无显著性差异.用"头皮包埋式"埋置法所采集的脑电信号数据显示,戊巴比妥麻醉的药理作用对大鼠和小鼠各频段相对功率值的影响无统计学差异,但θ,α和β波的相对功率值存在增加的趋势.进一步研究发现,θ,α和β波的相对功率随周龄增加显著升高(P<0.05),而δ波的相对功率无明显变化.结论 "头皮包埋式"埋置法操作简单方便,电极装置更加稳固,保持持久,能够有效采集脑电信号,可在大鼠和小鼠脑电测定相关实验中推广应用.

Behavioural sensitization (BS) is characterized by enhanced psychomotor responses to a dose of substance of abuse after prior repeated exposure. We previously reported that BS can be induced by a single injection of morphine in rats, whereas septal nuclei are specifically involved in the development phase of BS. Here, we demonstrated that intra-LS or intra-MS microinjections also incubated BS to a systemic morphine injection in a cross-sensitization fashion, whereas inactivation of either subdivision of septal nuclei (LS: lateral septum; MS: medial septum) can negate this ability of morphine. Then, non-selective (naloxone) and selective (μ-, δ- and κ-)opioid receptor antagonists were directly delivered into LS or MS, respectively, ahead of a morphine microinjection, whereas only μ-opioid receptors in both LS and MS play indispensable roles in mediating the BS development. Finally, there was a pronounced elevation in the levels of the monoamines (i.e. dopamine, homovanillic acid, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid) in the septum, 8 h after a morphine injection detected with a HPLC-ECD method, suggesting that dopaminergi and serotoninergic systems are implicated in the BS formation. Our studies demonstrated that septal nuclei critically participate in the BS development. Essentially, μ- instead of δ- or κ-opioid receptors in LS and MS mediate sensitization to opiates.

焦虑障碍是我国成人患病率最高的精神疾病,但其治疗药物的研发却一直滞后于该疾病的医疗需求.目前临床常用的抗焦虑药物主要包括部分苯二氮类药物、非苯二氮类药物和部分抗抑郁药,大多具有令人不快的副作用.该文通过检索Pubmed的文献资料,从内源性大麻素系统、肠-微生物-脑轴和GABAA受体亚基3个角度切入,总结介绍近年新型抗焦虑药物的研究进展,希望能够为该领域的发展提供帮助.

风险评估(RA)是动物针对潜在威胁性刺激演化形成的一种适应性机制,能够帮助动物定位刺激来源、获得刺激相关特征并对潜在危险做出最佳的防御反应.RA过程失调和损害所致的个体表现与焦虑障碍的临床症状相似,并可能与其发病存在直接联系.抗焦虑药物能够显著降低动物模型中RA行为发生的频率,进一步揭示了RA行为与焦虑之间的关系.然而,作为一种可量化的行为学指标,RA虽比传统测量项目对抗焦虑药物检测更灵敏,却很少被采用.本文简要总结了RA行为的功能、神经生物学机制、药理学特征及其在焦虑动物行为学模型中的应用,以期为相关领域的研究提供理论依据.

目的 观察和比较梁氏情境应激箱对小鼠抑郁样行为的诱导作用,对其表观效度进行评价.方法将小鼠放入4种不同应激环境中15 min,随后采用饮糖偏爱实验、社交行为实验、新奇抑制摄食实验以及强迫游泳实验,评价4种情境应激环境对小鼠抑郁样行为相关指标的影响.结果 ①与饲养鼠笼、正方形箱和三角形箱3种情境应激环境相比较,梁氏情境应激箱处理显著性降低ICR小鼠的饮糖偏爱率.此外,间隔3 d重复3次给予梁氏情境应激刺激仍能明显抑制小鼠的饮糖行为;②ICR和KM小鼠属于远交系动物,而C57BL/6J小鼠为近交系动物.梁氏情境应激箱处理对3种小鼠的社交行为均具有明显的抑制作用;③梁氏情境应激箱处理对小鼠新奇抑制摄食实验中进食潜伏期和强迫游泳实验中不动时间未见明显影响.结论梁氏情境应激箱处理可产生特定的情境应激反应,引起小鼠典型的抑郁样行为表现.作为一种新的抑郁动物模型及其实验方法,具有良好的表观效度.