Contribution of acetylcholine to visual cortex plasticity

Acetylcholine is involved in a variety of brain functions. In the visual cortex, the pattern of cholinergic innervation varies considerably across different mammalian species and across different cortical layers within the same species. The physiological effects of acetylcholine in the visual cortex display complex responses, which are likely due to cholinergic receptor subtype composition in cytoplasm membrane as well as interaction with other transmitter systems within the local neural circuitry. The functional role of acetylcholine in visual cortex is believed to improve the signal-to-noise ratio of cortical neurons during visual information processing. Available evidence suggests that acetylcholine is also involved in experience-dependent visual cortex plasticity. At the level of synaptic transmission, activation of muscarinic receptors has been shown to play a permissive role in visual cortex plasticity. Among the muscarinic receptor subtypes, the M(1) receptor seems to make a predominant contribution towards modifications of neural circuitry. The signal transduction cascade of the cholinergic pathway may act synergistically with that of the NMDA receptor pathway, whose activation is a prerequisite for cortical plasticity.     

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.     

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.     

普萘洛尔修复即刻消退产生的二次创伤

恐惧消退能力的受损是创伤后应激障碍(posttraumatic stress disorder, PTSD)的标志之一。以往的研究表明, 相较于延迟消退, 恐惧获得后短时间内进行的消退训练不能形成长时程的消退记忆, 这一现象被称为即刻消退缺损。然而, 目前并不清楚这种缺损是一次性的, 还是会继续影响其后的重消退。实验1中, 大鼠在恐惧习得后1小时(即刻消退)或24小时(延迟消退)开始进行消退训练, 24小时后进行重消退, 再24小时后进行消退记忆的测试。结果显示, 与延迟消退相比, 即刻消退效果缺损, 并引起第二天的重消退也出现效果缺损。实验2中, 恐惧获得后立即给予大鼠盐水或β-肾上腺素受体阻断剂普萘洛尔(10 mg/kg, i.p.), 然后测试即刻消退和重消退的效果。结果显示, 普萘洛尔虽没有阻止即刻消退的缺损, 但避免了重消退出现缺损。总之, 严重创伤后的即刻消退不但无法有效抑制恐惧反应, 还可能造成二次创伤, 会损害恐惧消退能力, 而普萘洛尔可修复即刻消退引起的重消退缺损。这些结果将有助于我们加深对PTSD病理机制和早期干预后果的认识。     

多巴胺D2受体参与调节感觉门控的机制

精神分裂症是一种常见的病因不明的精神疾病。大量文献表明精神分裂症患者所表现出来的认知紊乱和思维异常等症状与感觉门控功能的缺失有密切的关系, 感觉门控是指在充满刺激的环境中, 从外界的感觉信息中过滤无关的感觉信息然后执行与注意力相关的认知过程, 以对显著的刺激做出反应。研究感觉门控的经典范式是震惊反射的前脉冲抑制。研究发现多巴胺D₂受体可以参与调控前脉冲抑制的过程, 但是多巴胺D₂受体参与调控前脉冲抑制的机制仍不清楚。探讨多巴胺D₂受体参与调控感觉门控即前脉冲抑制的关键脑区、神经环路及分子机制, 有利于促进对精神分裂症感觉门控功能的深入研究。