Endogenous opioid peptides contribute to associative LTP in the hippocampal CA3 region

The medial and lateral perforant path projections to the hippocampal CA3 region display distinct mechanisms of long-term potentiation (LTP) induction, N-methyl-d-aspartate (NMDA) and opioid receptor dependent, respectively. However, medial and lateral perforant path projections to the CA3 region display associative LTP with coactivation, suggesting that while they differ in receptors involved in LTP induction they may share common downstream mechanisms of LTP induction. Here we address this interaction of LTP induction mechanisms by evaluating the contribution of opioid receptors to the induction of associative LTP among the medial and lateral perforant path projections to the CA3 region in vivo. Local application of the opioid receptor antagonists naloxone or Cys2-Tyr3-Orn5-Pen7-amide (CTOP) normally block induction of lateral perforant path-CA3 LTP. However, these opioid receptor antagonists failed to block associative LTP in lateral perforant path-CA3 synapses when it was induced by strong coactivation of the medial perforant pathway which displays NMDAR-dependent LTP. Thus strong activation of non-opioidergic afferents can substitute for the opioid receptor activation required for lateral perforant path LTP induction. Conversely, medial perforant path-CA3 associative LTP was blocked by opioid receptor antagonists when induced by strong coactivation of the opioidergic lateral perforant path. These data indicate endogenous opioid peptides contribute to associative LTP at coactive synapses when induced by strong coactivation of an opioidergic afferent system. These data further suggest that associative LTP induction is regulated by the receptor mechanisms of the strongly stimulated pathway. Thus, while medial and lateral perforant path synapses differ in their mechanisms of LTP induction, associative LTP at these synapses share common downstream mechanisms of induction.     

Cholinergic dependence of taste memory formation: evidence of two distinct processes

Learning the aversive or positive consequences associated with novel taste solutions has a strong significance for an animal's survival. A lack of recognition of a taste's consequences could prevent ingestion of potential edibles or encounter death. We used conditioned taste aversion (CTA) and attenuation of neophobia (AN) to study aversive and safe taste memory formation. To determine if muscarinic receptors in the insular cortex participate differentially in both tasks, we infused the muscarinic antagonists scopolamine at distinct times before or after the presentation of a strong concentration of saccharin, followed by either an i.p. injection of a malaise-inducing agent or no injection. Our results showed that blockade of muscarinic receptors before taste presentation disrupts both learning tasks. However, the same treatment after the taste prevents AN but not CTA. These results clearly demonstrate that cortical cholinergic activity participates in the acquisition of both safe and aversive memory formation, and that cortical muscarinic receptors seem to be necessary for safe but not for aversive taste memory consolidation. These results suggest that the taste memory trace is processed in the insular cortex simultaneously by at least two independent mechanisms, and that their interaction would determine the degree of aversion or preference learned to a novel taste.     

Tuning the engine of cognition: a focus on NMDA/D1 receptor interactions in prefrontal cortex

The prefrontal cortex of the primate frontal lobes provides the capacity for judgment which can constantly adapt behavior in order to optimize its outcome. Adjudicating between long-term memory programs and prepotent responses, this capacity reviews all incoming information and provides an interpretation dependent on the events that have just occurred, the events that are predicted to happen, and the alternative response strategies that are available in the given situation. It has been theorized that this function requires two essential integrated components, a central executive which guides selective attention based on mechanisms of associative memory, as well as the second component, working memory buffers, in which information is held online, abstracted, and translated on a mental sketchpad of work in progress. In this review, we critically outline the evidence that the integration of these processes and, in particular, the induction and maintenance of persistent activity in prefrontal cortex and related networks, is dependent upon the interaction of dopamine D1 and glutamate NMDA receptor signaling at critical nodes within local circuits and distributed networks. We argue that this interaction is not only essential for representational memory, but also core to mechanisms of neuroadaptation and learning. Understanding its functional significance promises to reveal major new insights into prefrontal dysfunction in schizophrenia and, hence, to target a new generation of drugs designed to ameliorate the debilitating working memory deficits in this disorder.     

Inhibition of aggression by progesterone and its metabolites in female Syrian hamsters

The sequence of estradiol and progesterone is known to inhibit the expression of aggression in female hamsters. Despite the key importance of progesterone in the inhibition of aggression, little is known of the mechanisms through which progesterone may exert this effect. Three experiments were performed to assess the degree to which metabolites of progesterone can affect aggression in female Syrian hamsters. Systemic estradiol treatment followed by injections of either progesterone (300 μg IP) or 4‐pregnen‐21‐ol‐3,20‐dione (DOC, 300 μg IP) reliably inhibited aggression. Systemic injection (75, 150, or 300 μg IP) of either 5α‐pregnan‐3α,21‐diol‐20‐one (THDOC) or 5α‐pregnan‐3α‐ol‐20‐one (3α,5α‐THP) did not affect aggression. Intracerebroventricular infusion of 3α,5α‐THP following systemic estradiol treatment also did not affect aggression. In a third experiment, female hamsters were given systemic treatments with estradiol and progesterone that were subthreshold with respect to inhibition of aggression. In these females, intracerebroventricular infusion of THDOC inhibited aggression. These results indicate that metabolites of progesterone can inhibit aggression, most notably in synergy with progesterone itself. Aggr. Behav. 27:372–381, 2001. © 2001 Wiley‐Liss, Inc.     

中枢白细胞介素-1在应激升压反应中的作用

分别在乌拉坦麻醉及清醒的雄性SD大鼠观察到：(1)脑室注射IL-113出现升压效应,(2)条件恐惧应激刺激、足电击及脑室注射IL-1β诱发的升压反应均被脑室注射0．5pg的白细胞介素-1拮抗剂IL-1ra明显衰减;(3)静脉注射0．5μgIL-1ra对足电击引起的升压反应无明显影响。以上结果提示中枢IL-1介导条件恐惧应激刺激、及足电击诱发的升压反应。     

不同5-HT3受体拮抗剂预防腹腔镜术后恶心呕吐的临床观察

观察使用不同5-HT3受体拮抗剂预防全麻下腹腔镜手术术后恶心呕吐的临床效果。选择160例气管内插管全身麻醉下腹腔镜手术,随机分四组,每组40例,手术结束前30min分别静脉注射昂丹司琼4mg（A组）;托烷司琼2mg（B组）;格拉司琼3mg（C组）;D组为对照组。记录术后2h、6h、12h、24h患者恶心、呕吐出现的例数。结果四组患者术后恶心呕吐的发生率是一个逐渐下降的趋势,A、B、C三组与D组相比较有显著性差异（P〈0．05）;术后2h、6h、12hB组与A组、C组相比较有显著性差异（P〈0．05）;而术后24hA、B、C三组差异无统计学意义,A、B、C三组抑制恶心呕吐的有效率分别为67．5％、87．5％和70．0％,与对照组比较差异有统计学意义（P〈0．05）,随访患者24h内无与药物相关的不良反应。结论：三种药物都能有效地预防术后恶心呕吐,但12h内托烷司琼的有效性更为明显。     

晚期非小细胞肺癌TKIs治疗：关注与思考

以表皮生长因子受体（EGFR）为靶点的酪氨酸激酶抑制剂（TKIs）对晚期非小细胞肺癌EGFR突变患者的治疗效果令人瞩目。本文分析总结近年国内外相关研究,指出低剂量TKIs的应用虽有待进一步证实,但优于标准剂量组,并从安全性、改善肿瘤血管结构和功能、与细胞毒化疗的关系三方面探讨大剂量TKIs的应用效果。进一步分析指出大剂量联合小剂量TKIs能够最大程度地防止或延迟耐药的发生,进而控制疾病的进展。从而,为晚期非小细胞肺癌EGFR突变患者的TKIs治疗选择提供参考。     

Role of cholinergic system on the construction of memories: taste memory encoding

There is a large body of evidence suggesting that cholinergic activity is involved in memory processes. It seems that cholinergic activity is essential to learn several tasks and recent works suggest that acetylcholine plays an important role during the early stages of memory formation. In this review, we will discuss the results related to taste memory formation, focusing particularly on the conditioned taste aversion paradigm. We will first give evidence that nucleus basalis magnocellularis is involved in taste memory formation, due to its cholinergic projections. We then show that the cholinergic activity of the insular (gustatory) cortex is related to the taste novelty, and that the cholinergic signals initiated by novelty are crucial for taste memory formation. Then we present recent data indicating that cortical activation of muscarinic receptors is necessary for taste trace encoding, and also for its consolidation under certain circumstances. Finally, interactions between the cholinergic and other neuromodulatory systems inducing intracellular mechanisms related to plastic changes will be proposed as important processes underlying gustatory memory trace storage.     

前列腺素E2及其在肾脏调控中的作用

前列腺素E2(PGE2)是最主要的前列腺素化合物,参与几乎所有的细胞代谢活动并介导多种不同的生理病理功能。PGE2的生物学效应是通过与不同的EP受体结合从而激活不同的信号转导通路来实现的。因为各类EP受体在肾脏的高分布,所以近来PGE2在肾脏中的作用日趋引起人们的重视。     

维生素D_3及其受体的临床意义

1,25-(OH)2D3是维生素D在体内发挥生理作用的活性形式。活性维生素D3通过与细胞内特异性维生素D受体结合,除了具有调节钙磷代谢的功能外,还发现其可预防和治疗骨质疏松、心血管疾病、自身免疫性疾病和一些肿瘤等。然而,维生素D缺乏在人群中非常普遍。