Characterization of the discriminative stimulus effects of lorcaserin in rats

Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5‐HT)_2C receptors and might also have agonist properties at other 5‐HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague–Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed‐ratio 5 schedule for food. Lorcaserin (0.178‐1.0 mg/kg) dose‐dependently increased lorcaserin‐lever responding. The 5‐HT_2C receptor agonist mCPP and the 5‐HT_2A receptor agonist DOM each occasioned greater than 90% lorcaserin‐lever responding in seven of eight rats. The 5‐HT_1A receptor agonist 8‐OH‐DPAT occasioned greater than 90% lorcaserin‐lever responding in four of seven rats. The 5‐HT_2C receptor selective antagonist SB 242084 attenuated lorcaserin‐lever responding in all eight rats and the 5‐HT_2A receptor selective antagonist MDL 100907 attenuated lorcaserin‐lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5‐HT_2C receptors, lorcaserin also has agonist properties at 5‐HT_2A and 5‐HT_1A receptors. Because some drugs with 5‐HT_2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders.     

Muslim–Paulician Encounters and Early Islamic Anti-Christian Polemical Writings

This article investigates the portrayals of the Paulicians in early Islamic sources and specifically analyses the role that Paulician religious views play in Islamic anti-Christian writings. The study also gives insights into the nature of materials that were available to Muslim scholars and the strategies they applied in constructing coherent arguments to refute certain Christian religious beliefs. In doing so, the study touches upon Muslims’ religious needs and scholarly curiosity, which sheds light on their intellectual interactions with non-Islamic religious beliefs and philosophical ideas. The article demonstrates that references to Paulician religious beliefs can be found primarily in early Christian–Islamic polemics. Muslim polemicists, most of whom were Mu?tazilites, attempted to demonstrate the soundness and the coherence of Islamic tenets vis-à-vis inadequacies and contradictions in Christian doctrines. The reliance of Muslim polemicists on heresiographical discourse therefore constituted an important strategy to substantiate their polemical arguments. Two major issues stand out in Islamic portrayals of Paulician doctrines: the centrality of Paul of Samosata in the history of the sect, and his association with the view that Jesus was a human being devoid of divinity.     

关于《上清经》

本文探讨《上清经》与上清派的命名、《上清原统经目注序》的撰作时间和作者以及东晋《上清经》的成书等问题。着重考察了华侨、杨羲、许谧、许翽等制作的首批上清经、传、诰的情况,并列书名、篇目;同时指出《上清经》的某些复杂性质。本文对与经书相关的道教分派标准问题也提出了自己的见解。     

药物成瘾机制与手术戒毒研究进展

本文从神经束路学、神经生理学、神经化学和分子神经生物学等方面分析了药物成瘾的病理生理学机制。探讨了立体定向手术戒毒的理论依据及发展方向：通过射频毁损或脑深部电刺激,部分破坏或抑制脑内异常兴奋点,阻断药物刺激引起的病理性信息传递,进而打破药物引起的病理性平衡,通过脑功能的代偿作用和手术后适当的心理行为康复治疗使成瘾相关环路在新水平上重建相对健康的平衡,进而达到减轻药物心理依赖、降低复吸率的目的。     

关于手术戒毒规范化开展的思考

吸毒成瘾是严重的医学和社会学问题。国内、外对吸毒成瘾采取的治疗方案由脱毒、防复吸和回归社会三个相互关联的方法构成。但收效甚微,复吸率居高不下。西安第四军医大学唐都医院神经外科在动物实验和借鉴以往经验的基础上,将立体定向技术用于毁损脑内与毒品心理依赖密切相关的关键位点的异常部分,对其异常功能进行调整,从而达到彻底戒毒的目的,取得了良好的疗效。本文介绍了手术戒毒在我国的发展历史,提出了规范化开展手术戒毒的建议。     

Behavioral profile of L–741,741, a selective D4 dopamine receptor antagonist,in social encounters between male mice

Although the role of dopamine D1–D2–D3 receptors in the modulation of aggression has been extensively documented, there is not information with respect to the implication of D4 receptor. The aim of this study was to examine the acute effects of L–741,741 (0.75, 1.5 and 3 mg/kg, i.p), a selective D4 receptor antagonist, on social encounters between male mice using an ethopharmacological approach. Ten min of diadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. These encounters were videotaped and the accumulated time allocated by subjects to ten broad behavioral categories was estimated. Besides other behaviors, the aggressive and motor behaviors were evaluated 30 min after injection using an ethologically based analysis. L–741,741 did not affect significantly offensive behaviors (threat and attack), as compared with the control group. Likewise, motor and anxiety‐related behaviors (such as social investigation, avoidance/flee or defense submission) were not altered after drug administration. These results suggest that dopamine D4 receptor is not involved in the modulation of aggressive behavior. Aggr. Behav. 29:552–557, 2003. © 2003 Wiley‐Liss, Inc.     

NMDA受体的结构与药理学特性

NMDA受体是一类离子型谷氨酸受体,其功能主要参与发育过程中神经回路的细化及触发多种形式的突触可塑性。近年来的证据表明,组成NMDA受体的亚单位有着复杂的生理学和药理学特性;NMDA受体的数量、分布和亚单位组成并非一成不变,而是在发育过程中、神经元活动时,以一种细胞特异性和突触特异性的方式变化着。这种NMDA受体的双向变化是突触可塑性重塑的基础,而其调节的异常又可导致神经-精神疾病的发生,如可卡因成瘾、精神分裂症等     

β-受体阻滞剂治疗慢性心力衰竭的哲学发展观

随着科学技术的快速发展和人们认识的不断深入,慢性心力衰竭（CHF）的发病机制处于不断嬗变的过程,CHF的药物治疗概念也发生了根本性的变化。β-受体阻滞剂在CHF的治疗策略中,经历了从禁用到必用的过程,成为了CHF药物治疗的重大突破。大量临床试验表明,β-受体阻滞剂不仅能改善患者预后,而且能明显改善左室的舒张和收缩功能,全面改善患者的血流动力学,提高患者的运动耐量和生活质量,延长生存时间。β-受体阻滞剂在CHF治疗中地位的变化,体现了哲学发展观与疾病的治疗以及药物应用的紧密联系,指导着我们的临床实践,也体现了哲学与自然科学的密切联系。本文将β-受体阻滞剂治疗CHF的新旧观念进行阐述、比较,对其作用机制以及临床用药进行介绍,并对其发展空间进行展望。随着科学的进步,人类有能力从长远的角度控制疾病。     

Treadmill exercise enhances passive avoidance learning in rats: the role of down-regulated serotonin system in the limbic system

While serotonin (5-HT) may impair learning and memory, exercise has been reported to improve them. Whether chronic exercise can facilitate fear memory via regulating the serotonin system is unknown. We examined the effects of 4-week treadmill exercise training on levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), the protein expression of its receptor 5-HT_1A and transporter in the amygdala, hippocampus and prefrontal cortex of male Sprague–Dawley rats. Our results demonstrated that treadmill exercise (1) improved the passive avoidance learning performance; (2) decreased the 5-HT level in the hippocampus; (3) decreased the expression of 5-HT_1A receptor in the amygdala without altering the transporter expression. Moreover, pretreatment with 0.1 mg/kg 8-hydroxy-di-n-propylamino tetralin, a selective 5-HT_1A receptor agonist, impaired the passive avoidance performance and completely abolished the exercise-enhanced fear memory. Our results suggest that down-regulation of the 5-HT system in the limbic system, i.e., the reduction of the hippocampus 5-HT content and the amygdala 5-HT_1A receptor expression, may be involved in the exercise-enhanced fear memory.     

“Cuts in Action”: A High‐Density EEG Study Investigating the Neural Correlates of Different Editing Techniques in Film

In spite of their striking differences with real‐life perception, films are perceived and understood without effort. Cognitive film theory attributes this to the system of continuity editing, a system of editing guidelines outlining the effect of different cuts and edits on spectators. A major principle in this framework is the 180° rule, a rule recommendation that, to avoid spectators’ attention to the editing, two edited shots of the same event or action should not be filmed from angles differing in a way that expectations of spatial continuity are strongly violated. In the present study, we used high‐density EEG to explore the neural underpinnings of this rule. In particular, our analysis shows that cuts and edits in general elicit early ERP component indicating the registration of syntactic violations as known from language, music, and action processing. However, continuity edits and cuts‐across the line differ from each other regarding later components likely to be indicating the differences in spatial remapping as well as in the degree of conscious awareness of one's own perception. Interestingly, a time–frequency analysis of the occipital alpha rhythm did not support the hypothesis that such differences in processing routes are mainly linked to visual attention. On the contrary, our study found specific modulations of the central mu rhythm ERD as an indicator of sensorimotor activity, suggesting that sensorimotor networks might play an important role. We think that these findings shed new light on current discussions about the role of attention and embodied perception in film perception and should be considered when explaining spectators’ different experience of different kinds of cuts.