Anti-conflict effects of benzodiazepines in rhesus monkeys: relationship with therapeutic doses in humans and role of GABAA receptors

Rationale and Objectives Conflict procedures are used to study mechanisms underlying the anxiolytic effects of benzodiazepines (BZs). We established a conflict procedure with rhesus monkeys in order to examine the role of GABA_A receptors in the anxiolytic-like effects of BZs. Methods Four rhesus monkeys responded under a two-component multiple schedule in which responding was maintained under a fixed-ratio schedule of food delivery in the absence (non-suppressed responding) and presence (suppressed responding) of response-contingent electric shock. Results Conventional BZs (alprazolam, flunitrazepam, clonazepam, nitrazepam, lorazepam, bromazepam, diazepam, flurazepam, clorazepate, chlordiazepoxide) engendered increases in the average rates of suppressed responding at low to intermediate doses and decreased the average rates of non-suppressed responding at higher doses. Positive correlations were observed when the therapeutic potencies of BZs in humans were compared with potencies to increase the rates of suppressed responding (R ²=0.83) or decrease the rates of non-suppressed responding (R ²=0.60). The 5-HT_1A agonist buspirone increased the rates of suppressed responding, although the effects were modest, whereas the opioid morphine lacked anti-conflict effects. The BZ antagonist flumazenil also modestly increased the rates of suppressed responding. A relatively low dose of flumazenil enhanced, while a high dose blocked, alprazolam’s anti-conflict effects. Compounds selective for α₁ subunit-containing GABA_A receptors (zolpidem, zaleplon, CL218,872) engendered relatively weak increases in the rates of suppressed responding. Conclusions A rhesus monkey conflict procedure was established with predictive validity for therapeutic doses in people and provided evidence that anxiolytic-like effects of BZs can occur with relatively low intrinsic efficacy at GABA_A receptors and are reduced by α₁GABA_A receptor selectivity. This research was supported by U.S.P.H.S. grants DA11792 and RR00168     

Antagonism of morphine by long acting narcotic antagonists

Thirty-six female albino rats, trained to run for a chocolate reward in a circular runway, were treated according to 6×6 Latin square schemes with five doses of 3-quinuclidinylbenzilate, ranging from 0.1 to 10 mg/kg, or the vehicle. On experimental days there were 6 consecutive trials. Intraperitoneal injections were administered 20 min before the first trial. The apparatus was automated as far as the opening of sliding doors and the recording of the duration of running, subdivided into latency and running-time, were concerned. Along with the duration of running, the behaviour shown in the various parts of the maze was analysed. The drug caused a marked, dose-dependent increase of the latency, whereas the effect on running-time was comparatively small. During the latency the frequency of ambivalent behaviours, shown at the transition of the start-goal compartment and the runway, increased under the influence of 1 mg/kg or more. Concomitant increases were noted in the frequency of displacement activities, which were absent in control animals. The results were interpreted as a drug-induced intensification of a conflict, existing in normal animals between the tendency to stay in the vicinity of the reward and the tendency to run for a subsequent reward.     

Mechanisms of the initial treatment phenomenon to diazepam in the rat

The initial treatment phenomenon (ITP) to diazepam was investigated using a conditioned suppression of drinking (CSD) paradigm. Female Sprague-Dawley rats were trained to a stable baseline of punished and unpunished responses in the CSD paradigm. In Experiment 1, a control group (1) received vehicle after the CSD session on each of seven drug test days, while group 2 was treated with 3.0 mg/kg diazepam IP after each of these sessions. On drug test days 8–12, diazepam was administered to both groups before the CSD session. Drug test days were separated by 2–3 days when the animals were untreated but performed in the CSD. Prior exposure to diazepam in group 2 after sessions 1–7 conditioned the animals so that a greater release in punished behavior was seen during sessions 8–12 than in the control group (1). In Experiment 2, one group (3) of rats was administered diazepam vehicle after the CSD session for 4 drug test days and another group (4) was injected with 5.6 mg/kg diazepam after the CSD session on these same days. On the next 4 drug test days both groups received diazepam before they performed in the CSD. An ITP was observed in both the control (3) and the drug-conditioned (4) group, although the ITP was less obvious in the conditioned group. After a 28-day period of CSD exposure without vehicle or drug treatments, 5.6 mg/kg diazepam was administered to both groups before the CSD session for an additional 8 drug test days. During this last period both groups exhibited an ITP with no essential differences. These experiments demonstrate that the initial treatment phenomenon is complex, involving several components that include a behavioral tolerance to the disruptive effect of diazepam.     

试论医疗服务中的冲突

医疗服务活动中存在着多种冲突,如医疗保护制度与患者知情同意权及隐私权之间的冲突、医疗风险与患者利益的冲突及医疗效果与患者就医期望值的冲突等。医疗行为的不确定性,结果的转归具有不可控性等因素决定冲突是必然存在的。此外,医务人员为规避风险采取自我保护的行为,医患双方沟通不畅等是产生冲突的主观因素。而现行的医疗制度是冲突存在的客观原因。解决冲突应从完善制度、规范行为,加强医患沟通等方面着手。     

ICU年轻护士角色冲突和角色模糊、工作疲溃感对离职意愿的影响

目的 探讨ICU年轻护士角色冲突和角色模糊、工作疫渍感对离职意愿的影响.方法 采用角色冲突和角色模糊、工作疲溃感和离职意愿量表,对济南市6家综合性医院的144名ICU年轻护士进行调查.结果 ICU年轻护士的角色冲突和角色模糊、工作疲溃感与离职意愿均呈显著正相关,情绪疲溃感、工作冷漠感和角色模糊对其离职意愿有显著影响.结论 管理者应针对ICU年轻护士离职意愿的影响因素,采取相应的干预措施以降低离职率,稳定护理队伍.     

The time course of alerting effect over orienting in the attention network test

In the present experiment we used a version of the attention network test (ANT) similar to that of Callejas et al. (Exp Brain Res 167:27–37, 2005) to assess the Posner’s attention networks (alerting, orienting and conflict), and their interactions. We observed shorter reaction times with alerting tone than with no alerting tone trials (the alerting effect); with cued than with uncued trials (the orienting effect); and with congruent than with incongruent trials (the conflict effect). These results replicate previous findings with the ANT. We also manipulated cue–target interval at five stimulus onset asynchrony (SOA) values (100, 300, 500, 800, and 1,200 ms) to trace the alerting network influence over the orienting network. The SOA manipulation showed that cuing effects peaked at 300 ms SOA irrespective of whether an alerting tone was present or not, and the alerting tone improved the cuing effect equally for 100–500 SOAs, but it did not at the longest 800–1,200 ms SOAs. These results suggest that alerting improves rather than accelerates orienting effects, a result that agrees with data from neuropsychological rehabilitation of parietal patients with spatial bias.

护士长管理冲突模型的构建

目的构建护士长管理冲突模型,为护士长的选拔培训提供依据。方法通过理论研究、质性访谈、小组会议,初步纳入护士长管理冲突的影响因素;选取并修订相应量化工具;采用整群抽样对上海市486名护士长进行实测。结果模型最终纳入护士长的情绪调节能力、识别他人情绪能力和整合、支配、妥协3种冲突处理型态;所建模型拟合度较好。结论护士长的情绪智力和冲突处理型态是护士长管理冲突的影响因素。     

Reward valence modulates conflict-driven attentional adaptation: electrophysiological evidence

Recent findings suggest that, relative to negative feedback, positive feedback counteracts conflict processing and subsequent attentional adaptation. Here we hypothesize that this interaction may direct adjustments in perception and action via the anterior cingulate cortex (ACC). We recorded EEG while participants performed an arrow flanker task with monetary gain or loss as arbitrary reward feedback between trials. As predicted, we found a reduction in conflict-driven adaptation for trials in which conflict was followed by monetary gain (vs. monetary loss), a behavioral effect accompanied by a modulation in early visual processing related to the processing of the distracters. Moreover, time-frequency analyses showed that ongoing fronto-central theta oscillations induced by previous conflict sustained longer after loss than after gain, an interaction presumably reflecting ACC modulation. These data provide a first important step toward understanding the neural mechanism underlying the affective regulation of conflict-driven behavior.     

Industry Funding Is Correlated With Publication Productivity of US Academic Radiation Oncologists

Purpose

Industry payments to physicians are financial conflicts of interest and may influence research findings and medical decisions. We aim to (1) characterize industry payments within radiation oncology; and (2) explore the potential correlation between receiving disclosed industry payments and academic productivity.