Neurotransmitters, anxiety and benzodiazepines: A behavioral review

The possible involvement of serotonin, GABA and opioid peptides in anxiety and in the mechanism of action of benzodiazepine tranquillizers have recently been the subjects of intensive biochemical, neurophysiological and behavioral research. The present review examines the behavioral evidence, viewing anxiety and benzodiazepine action as far as possible separately. Four behavioral paradigms of experimental anxiety or “conflict behaviors” are described and assessed for soundness with some practical considerations. The functional significance and pharmacology of benzodiazepine receptors are discussed, and the cases for a number of putative endogenous ligands are examined. Conflict behavior is attenuated by drugs which reduce functional serotonin activity and enhanced by serotonin agonists, but there is little evidence to implicate serotonin in benzodiazepine action. GABA antagonists both intensify conflict and reduce benzodiazepine effects, but evidence of the reverse effects with GABA agonists is more equivocal. The interpretation of behavioral effects of opiate agonists and antagonists and their interactions with benzodiazepines is hindered by their actions on motivational systems other than anxiety, and evidence for an important role of opioid peptides is only suggestive. Some promising lines for future research are indicated.     

基层医院儿科门诊注射室减少护患冲突的方法与评价

目的：提高护理人员的护患沟通技巧,以减少护患之间的冲突。方法：对儿科门诊注射室护士进行礼仪、专业知识、沟通技巧等培训,采用自行设计的护患沟通情况调查表,对在儿科门诊注射室治疗的患者及家属进行培训前（80例）和培训后（100例）的调查。结果：培训后护患关系、护士专业知识水平、沟通内容掌握程度、沟通技巧熟练程度等较培训前显著改善（P〈0.05,P〈0.01）。结论：进行护士沟通技巧培训对提高护患关系密切度及做好健康教育有重要的意义。     

Using virtual reality to explore the role of conflict resolution and environmental salience in Freezing of Gait in Parkinson's disease

BackgroundThe freezing phenomenon is among the most disabling symptoms of Parkinson's disease (PD) manifesting most commonly as Freezing of Gait with a paroxysmal cessation of effective stepping. Recent studies have suggested that freezing is related to both impairments in conflict resolution as well as the processing of environmentally salient information.MethodsIn this study, we utilized a virtual reality gait paradigm to investigate differences in motor outflow between PD patients with (n = 36) and without (n = 37) Freezing of Gait, as well as age-matched healthy controls (n = 18). Subjects were required to navigate a realistic on-screen environment with the use of foot pedals to simulate stepping whilst responding to either cues associated with conflict resolution (congruent ‘Red’, ‘Green’ or ‘Blue’) or environmental salience (wide, narrow and sliding doorways). Footstep latency was used as a measure of motor output.ResultsSignificantly increased stepping latencies were observed in freezers compared to non-freezers (p = 0.004) and controls (p = 0.016) in response to stimuli requiring the inhibition of implicitly cued behavior (‘red’ cue). Patients with Freezing of Gait also demonstrated increased motor latency compared to non-freezers and controls specifically in response to environmentally salient triggers including narrow doorways (p = 0.03 and 0.01 respectively) and the opening of a sliding door (p = 0.036 and 0.048 respectively). Performance on the paradigm in relation to these triggers correlated significantly with self-reported freezing severity.ConclusionThese results suggest that deficits in conflict resolution and visuospatial processing may reflect some of the neural mechanisms associated with freezing behavior and that these can be probed in a virtual reality environment.     

不同年级大学生生活应激比较研究

随着高考招生并轨的完成和高校毕业生走向市场、双向选择就业机制的逐步建立，对作为跨世纪的大学生的要求越来越高，使得在校大学生面临着竞争挑战、挫折、矛盾、冲突等多种压力，随之产生一系列应激生理、心理和行为反应。当压力过大，应激状态时间持续过长，势必会影响大学生的心动理健康状况。本研究对部分大学生在校所面临的生活应激体验及其反应进行了调查，以了解处在我国政治体制和经济体制改革的社会变迁过程中的大学生所面临的生活应激源及其产生的反应。1材料和被试1.1材料采用美国学者B.M．Gadzella1991年编制的“学生生活应…     

Behavioral suppression using intracranial reward and punishment: effects of benzodiazepines

Rats were chronically implanted with electrodes aimed at the lateral hypothalamus (LH) and the dorsal central gray (DCG) and trained to press a lever that delivered rewarding stimulation of the LH and punishing stimulation of the DCG. In this situation, both diazepam (5-20 mg/kg, PO) and bromazepam (2-10 mg/kg, PO) caused a marked dose-dependent increase of the lever pressing response in the punished period. In addition, the facilitation of lever pressing in unpunished period was also seen in diazepam (5 and 10 mg/kg). These results show that behavioral suppression on lever pressing maintained self-stimulation reward is inducible following DCG stimulation, and that benzodiazepines exhibit an anti-behavioral suppression effect in this situation.     

Effects of combined treatment with nortriptiline and lorazepam on conflict behavior and motility of rats

Lorazepam attenuated the suppressant effects of punishment on the response rate of rats in the multiple schedule of reinforcement devised by Geller and Seifter (1960). Nortriptiline alone was ineffective on punished responses. Both drugs, at certain dose levels, inhibited the nonpunished response. Combined treatment with the two drugs in a dose ratio of 1:20 attenuated the effects of punishment at all dose levels tested. The effects of the combination upon both punished and nonpunished responding was greater than might be accounted for by a simple additive effect of the individual treatments. Lorazepam and nortriptiline both induced a dose-related decrease in the locomotor activity of rats; when given together the 2 drugs antagonized each other.The results give an experimental support to the clinical observations about the usefulness of the benzodiazepine-antidepressant combination in certain depressive illnesses.     

Gamma-butyrolactone increases the rate of punished lever pressing by rats

Four rats lever pressed for food on a two component multiple FR-VI schedule of reinforcement. In the FR component a brief electric shock coincided with the presentation of food. After level pressing stabilized in the presence of the shock, drugs were administered in two phases. In Phase 1, one of four doses of either gamma-butyrolactone or sodium pentobarbital was injected before sessions. Both drugs increased lever pressing rates during the shocked component of the schedule at doses which did not affect lever pressing rates during the unshocked component. In Phase 2, one of four doses of a mixture of the two compounds was injected. The drug mixture increased rates of punished lever-pressing to levels similar to those reached in Phase 1. These results confirm previous findings for sodium pentobarbital and indicate that gamma-butyrolactone warrants further investigation into its behavioral properties.     

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     

Dose-related effects of ethanol on avoidance-avoidance conflict behavior in the rat

The effects of ethanol on avoidance-avoidance conflict behavior were examined, utilizing a 3-×-3 factorial design in which rats were trained and tested after drinking sugar-water solutions containing 0,3, or 6% ethanol. Avoidance tendencies were established by initially training rats to escape from electric shock fy running in one direction in a white alley, and in the opposite direction in a black alley. In subsequent shock free conflict tests, the rats were placed into an alley with one black wall and one white wall, an environment in which incompatible tendencies to avoid both ends of the alley were aroused. During training, ethanol decreased the speeds with which rats escaped shock. In the subsequent avoidance-avoidance conflict tests, rats that previously received shock escape training after drinking ethanol ran more slowly, and exhibited lower total movement and oscillation range scores than did animals trained after drinking plain sugar-water. Administration of ethanol just prior to the conflict tests resulted in dose-related increases in running speeds, total movement scores, and oscillation ranges. These results suggest that moderate doses of ethanol increased responding by differentially weakening conflicting avoidance tendencies.     

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.