The effects of compounds related to γ-aminobutyrate and benzodiazepine receptors on behavioural responses to anxiogenic stimuli in the rat: Punished barpressing

Rats were trained to press a bar for sucrose reward on a random-interval (RI) schedule and footshock punishment was then introduced for 3-min intrusion periods (signalled by a tone) on an independent RI schedule. Shock intensity was individually adjusted to produce stable intermediate levels of response suppression during the tone for each animal. Groups of animals were then allocated to a number of separate experiments in which they were systemically injected with anxiolytics (chlordiazepoxide HCl or sodium amylobarbitone), GABA antagonists (picrotoxin or bicuculline), the GABA_A agonist muscimol, the GABA_B agonist baclofen, an antagonist (RO 15-1788) at the benzodiazepine receptor and, an inverse agonist (FG 7142) at this receptor. The results showed that the alleviation of punishment-induced suppression of barpressing produced by chlordiazepoxide was blocked or partially blocked by RO 15-1788, picrotoxin and bicuculline but not by FG 7142; that picrotoxin (but not FG 7142) increased the suppression of responding by punishment; that neither muscimol nor baclofen affected responding on their own, but their combination weakly but reliably released punished responding from suppression; and that the anti-punishment effect of amylobarbitone was unaffected by either picrotoxin or bicuculline, though the barbiturate reversed the punishment-enhancing effect of picrotoxin. These results are discussed in the light of the hypothesis that anxiolytic behavioural effects are due to increased GABAergic inhibition.     

Discriminative stimulus properties of β-carbolines characterized as agonists and inverse agonists at central benzodiazepine receptors

The discriminative stimulus properties of three -carboline derivatives were studied in three groups of rats trained, respectively, to discriminate diazepam (2.5 mg/kg IP), chlordiazepoxide (CDP, 5 mg/kg IP) or pentylenetetrazol (PTZ, 15 mg/kg IP) from saline in standard procedures employing two-lever operant chambers. Two -carbolines, ZK 91296 and ZK 93423, substituted for the benzodiazepines in both CDP- and diazepam-trained rats. The neutral benzodiazepine antagonist Ro 15-1788 blocked the diazepam discriminative stimulus and the ability of ZK 91296 to substitute for diazepam. A third -carboline, FG 7142, was not identified as benzodiazepine-like in generalization tests in either diazepam- or CDP-trained rats, but when administered together with CDP antagonized the benzodiazepine discriminative stimulus. In rats trained to discriminate PTZ from saline (a discrimination which is thought to depend on the anxiogenic properties of PTZ) the PTZ cue was antagonized by diazepam and ZK 93423, and partially antagonized by ZK 91296. The PTZ cue generalized to FG 7142 and this generalization was partially antagonized by Ro 15-1788. These results suggest that the three -carbolines provide more than one kind of discriminative stimulus, consistent with the classification of ZK 93423 as an agonist at central benzodiazepine receptors, with ZK 91 296 as a partial agonist, and with FG 7142 as an inverse agonist. Pharmacologically, ZK 93 423 and ZK 91 296 may exhibit anxiolytic qualities, whereas FG 7142 produces anxiogenic effects.     

ZK 91296, a partial agonist at benzodiazepine receptors

ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl--carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.     

Duration of benzodiazepine clinical activity: Lack of direct relationship with plasma half-life

The anxiolytic activity and tolerance of two dosage schedules of prazepam, a long plasma half-life benzodiazepine, were compared under double-blind conditions in two groups of 10 inpatients each who met Research Diagnostic Criteria for Generalized Anxiety Disorder and presented chronic and severe symptomatology. Patients received prazepam 40 mg per day on one of two dosage schedules: 1) divided dosage (DD) - 10 mg in the morning and at noon and 20 mg in the evening; or 2) single dosage (SD) - 40 mg in the evening. The 3 weeks of therapy were preceded and followed by 1 week of wash-out for baseline and follow-up assessments, which were performed weekly with the Hamilton Anxiety Scale, Clinical Global Impression, rating of morning drowsiness and evening worsening of symptoms, and patient self-rating of anxiety by means of a visual analogue scale performed both in the morning and in the afternoon. The results showed a clear superiority of the DD over the SD schedule: better anxiolytic efficacy on the Hamilton Anxiety Scale (P<0.0005) and on both morning and afternoon visual analogue scales (P<0.01 andP<0.0002); less morning drowsiness (P<0.0001); and steadier anxiolytic effect during the daytime, as globally rated by the investigator (P<0.0001) or measured by morning-afternoon differences on the visual analogue scale (P<0.005). These results suggest that plasma pharmacokinetics alone may not be sufficient to predict the duration of benzodiazepine anxiolytic activity.     

产褥期乳腺炎影响因素分析

目的探讨导致产妇发生产褥期乳腺炎(PM)的影响因素。 方法选择2020年9月1日至12月31日,在成都市某三甲妇女儿童医院分娩,并进行产后42 d随访的1 162例产妇为研究对象。根据产妇产后42 d内是否发生PM,将其分为PM组(n＝103)与对照组(n＝1 059)。采用本研究自行设计的《产褥期乳腺炎相关影响因素调查问卷》(以下简称为《调查问卷》),联合《中国简式心理状态剖面图(POMS)量表》(以下简称为《POMS量表》),分别对2组产妇进行调查。《调查问卷》内容主要包括产妇一般人口学资料、妊娠及疾病、药物使用、母乳喂养、饮食及生活习惯等10个维度,共计50个条目。《POMS量表》包括心理焦虑等7个维度,共计40个条目。对2组产妇《调查问卷》条目及《POMS量表》评分,采用独立样本t检验、χ²检验及Fisher确切概率法等进行统计学比较。本研究遵循的程序符合病例收集医院医学伦理委员会要求,经过该伦理委员会批准[审批文号：科研伦审2021(29)],并与研究对象签署临床研究知情同意书。2组产妇的年龄等一般临床资料比较,差异无统计学意义(P>0.05)。 结果①本研究纳入产妇的PM发生率为8.9%(103/1 162),产后第3、4周PM发生率最高,分别为2.7%(31/1 162)与2.4%(28/1 162)。②本研究2组产妇围生期补充铁剂及口服益生菌占比,乳头皲裂程度、吸奶器使用时间及频率、乳头保护罩与乳头保护霜使用频率构成比,哺乳衔接姿势正确率,哺乳时乳房疼痛程度、哺乳内衣穿戴率等分别比较,差异均有统计学意义(P<0.05)。③PM组产妇《POMS量表》焦虑评分为(7.1±5.0)分,显著高于对照组的(5.3±4.1)分,并且差异有统计学意义(t＝-3.540、P＝0.001)。④将上述影响产妇发生PM的单因素分析中差异有统计学意义因素,并结合已有研究结果与临床经验,纳入10项影响因素,进行多因素非条件logistic回归分析结果显示,产妇围生期补充铁剂(OR＝3.351,95%CI：1.949~5.758,P<0.001),乳头皲裂(OR＝3.564,95%CI：1.909~6.654,P<0.001),吸奶器使用频率>1次/d(OR＝5.102,95%CI：1.047~24.876,P＝0.044),乳头保护霜使用频率>1次/d(OR＝2.147,95%CI：1.156~3.987,P＝0.016),哺乳衔接姿势不正确(OR＝2.311,95%CI：1.202~4.445,P＝0.012),穿戴不舒适哺乳内衣(OR＝2.322,95%CI：1.008~5.347,P＝0.048),不穿戴哺乳内衣(OR＝3.516,95%CI：1.821~6.789,P<0.001),焦虑评分高(OR＝1.073,95%CI：1.007~1.143,P＝0.029),均为导致产妇发生PM的独立危险因素;而围生期口服益生菌(OR＝0.110,95%CI：0.025~0.478,P＝0.003)是其独立保护因素。 结论通过制定临床干预措施,指导产褥期产妇纠正不正确行为,如围生期补充铁剂、吸奶器与乳头保护霜使用不当,哺乳内衣穿戴及哺乳行为不规范等,提倡产妇围生期口服益生菌,缓解产妇焦虑情绪,对预防产妇PM发生具有重要意义。     

高频重复经颅磁刺激联合认知行为治疗对脑卒中后焦虑和抑郁共病状态患者的影响

目的观察高频重复经颅磁刺激(rTMS)联合认知行为治疗对脑卒中后焦虑(PSA)、脑卒中后抑郁(PSD)共病状态患者的影响。 方法采用随机数字表法将160例脑卒中后焦虑抑郁状态患者分为对照组和观察组。两组患者均给予脑卒中常规治疗、抗抑郁药物治疗和认知行为治疗,对照组同时给予高频rTMS假刺激治疗,观察组则给予高频rTMS真刺激治疗。观察4周后2组患者抑郁症状、焦虑症状、睡眠质量、日常生活能力改善情况。 结果两组患者汉密尔顿抑郁量表(HAMD)评分、汉密尔顿焦虑量表(HAMA)评分、匹兹堡睡眠指数量表(PSQI)、改良Barthel指数(MBI)在治疗前差异无统计学意义(P均>0.05)。治疗4周后,对照组和观察组的HAMD评分、HAMA评分、PSQI较治疗前下降,差异有统计学意义(P均<0.05),其中观察组下降更为明显,与对照组相比,差异有统计学意义(P<0.05)。对照组和观察组MBI与治疗前相比,均有明显提高,差异有统计学意义(P<0.05),而观察组和对照组相比,观察组分数提高更显著,差异有统计学意义(P<0.05)。观察组治疗有效率为87.50%,高于对照组的71.25%。两组之间差异有统计学意义(Uc＝－3.45,P<0.001)。 结论高频rTMS治疗联合认知行为治疗和认知行为治疗均能有效改善PSA+PSD患者的焦虑抑郁症状、睡眠质量及日常生活能力,但高频rTMS治疗联合认知行为治疗的效果更加明显。     

新冠疫情期间检疫隔离人群焦虑和抑郁状况调查研究

目的了解新冠病毒疫情期间检疫隔离群体心理状况,为心理干预提供参考。方法调查纳入2020年4月7日-5月26日期间由境外或重点疫区进入深圳的定点酒店检疫隔离人员,隔离人员需在隔离开始24 h内完成心理筛查。共收集调查问卷2219份,最后得到1705人填写的合格问卷,有效回收率为76.8%。采用健康问卷抑郁量表(PHQ-9)、广泛性焦虑量表(GAD-7)对检疫隔离人群进行心理问题筛查,统计方法包括t检验、方差分析及Pearson相关性分析、Logistic回归等。结果检疫隔离者抑郁、焦虑的检出率分别是15.8%、14.8%,多元Logistic回归分析显示,女性(OR=1.526)和对隔离部分理解及不理解(OR=3.273;OR=3.148)是检疫隔离者焦虑的危险因素;经济条件一般及较好(OR=0.422;OR=0.305)是检疫隔离者焦虑的保护因素;女性(OR=1.323)和对隔离部分理解及不理解(OR=3.387;OR=3.153)是检疫隔离者出现抑郁的危险因素;经济条件一般及较好(OR=0.627;OR=0.373)是检疫隔离者抑郁的保护因素。结论新型冠状肺炎疫情期间,检疫隔离者出现不同程度的焦虑、抑郁表现,需重点加强对女性、经济条件差、对隔离态度较差人群的心理疏导与社会支持。     

国产万拉法新治疗肠易激综合征的初步临床研究

目的 观察国产新药万拉法新对肠易激综合征（IBS）及其伴随的焦虑和抑郁症状的临床治疗效果。方法 选择48例IBS患者,随机分为治疗组和对照组,分别服用万拉法新及硝苯地平进行为期4周的治疗,通过对IBS各项症状的改善率和总体改善率评定观察治疗效果。同时采用Zung编制的抑郁自评量表和焦虑自评量表进行评分观察治疗前后抑郁和焦虑的改善程度。结果 万拉法新对IBS的治疗总体改善率为80％,对照组为52．17％（P＜0．05）。万拉法新治疗前后焦虑和抑郁的改善程度经检验均有统计学意义（P＜0．01）。结论 单独应用万拉法新对IBS的总体治疗效果优于硝苯地平组,对改善伴随的焦虑和抑郁症状有明显的疗效。     

孕妇睡眠质量与焦虑、抑郁的相关性研究

目的,了解孕妇在妊娠期睡眠质量与焦虑抑郁情绪状态的相关关系。方法：采用匹茨堡睡眠质量指数量表,症状自评量表,状态－特质焦虑问卷,焦虑自评量表,抑郁自评量表定,对83例孕妇的睡眠质量,状态－－特质焦虑,焦虑和抑郁状态水平进行调查分析。结果：孕妇的睡眠质量,入睡时间,睡眠时间,白天功能与焦虑和抑郁情绪症状呈正相关（P＜0．05）;孕妇睡眠质量与状态焦虑呈正相关关系（P＜0．05）,而入睡时间与特质焦虑呈正相关关系（P＜0．05）,结论;孕妇妊娠期睡眠质量与焦虑和抑郁情绪症状有正相关关系。     

洛丁新合并黛安神治疗原发性高血压疗效观察

目的：通过干预焦虑情绪,提高与心理因素密切相关的原发性高血压的治疗效果。方法：将会诊中发现有明显焦虑情绪的66例原发高血压患者随机分为两组,均用洛丁新降压8周,第一组同步用抗焦虑药黛安神。结果：降压有效率分别是93．94％,60．61,结论：有焦虚情绪的第二组治疗效果明显低于第一组。