Neuropharmacological aspects of adaptive pain inhibition in murine “victims” of aggression

This review outlines recent research on a subset of physiological responses in murine “victims” or aggression. In a typical resident-intruder paradigm, the detailed study of intruders has revealed that exposure to conspecific attack (and related stimuli) is associated with two forms of analgesia which appear to be integral components of the murine defensive repertoire. In response to intense/enduring attack, intruder mice display a profound, long-lasting and opioid-mediated analgesia. This reaction is highly correlated with defensive immobility and may function to reduce involuntary cues to further attack. In contrast, the inhibition of pain reactivity in mice tested immediately upon the display of defeat is less intense, shorter-lasting, non-opioid in nature and may function to facilitate active defenses such as escape. As this form of pain inhibition is also evident in intruders exposed to the scent of an aggressive male conspecific, a possible anticipatory defensive function linked to mechanisms of anxiety has been proposed. This hypothesis is supported by 1) the prevention of defeat analgesia by a range of antianxiety drugs (benzodiazepines, 5-hydroxytryptamine_1A [5-HT_1A] receptor agonists, and 5-HT₃ receptor antagonists) and 2) the effects of social defeat on behavior in the elevated plusmaze model of anxiety. These findings are discussed in relation to coping mechanisms in murine “victims” of aggression. © 1995 Wiley-Liss, Inc.     

Effects of neonatal treatment with 1-(2,5-dimethoxy-4-lodophenyl)-2 aminopropane HCI (DOI) and ritanserin on agonistic behavior in adult male and female rats

The role played by the neonatal 5-hydroxytryptamine (5HT) system in the organization and sexual differentiation of adult agonistic behavior was investigated in rats. Focus was on the 5HT2 receptor subtype, which has been demonstrated to be involved in agonism control in the adult. 5HT2 activity was experimentally manipulated by administration of a specific agonist [1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI)] or antagonist (ritanserin) during the second week of life, when serotonin is known to concur to anatomical and behavioral sexual differentiation. Interactions between early 5HT2 activity, genetic sex, and neonatal circulating testosterone (T) were studied by administering the ligands to males, females, and androgenized females. At adulthood, the animals were tested for both aspects of agonism, i. e., aggression and defense, in a 20-min confrontation with an unfamiliar conspecific of the same sex, age, body weight, and social experience. Neonatal administration of the 5HT2 antagonist ritanserin increased aggression independently of sex; it also increased defense, but this effect was confined to males. The agonist DOI had no effect on aggression, but enhanced defense in males and androgenized females, with an effect which depended therefore more on neonatal T than genetic sex. Females appeared in general less sensitive to neonatal 5HT2 manipulation than both androgenized females and males; this suggests that neonatal T is crucial for experimental modifications of neonatal 5HT2 activity to have any consistent effect on adult agonistic behavior. On the other hand, effects observed in males and androgenized females were dependent on the behavior considered and the drug administered. This was especially evident for defense, enhanced by ritanserin in males only, and in both males and androgenized females by DOI. Neonatal 5HT2 activity seems therefore to play a role in the modulation of adult agonistic behaviors, which depends on the behavior considered and is under multiple control of genetic sex and hormonal neonatal substrate. © 1994 Wiley-Liss, Inc.     

Regulation of glutamate synapses by nicotinic acetylcholine receptors in auditory cortex

Acetylcholine plays an important role in regulating the processing of sensory stimuli, and understanding its specific cellular actions is critical to understanding how sensory cortex develops and functions in different behavioral states. Here we review recent work on the cellular effects of nicotinic receptor activation in auditory cortex and describe how these actions could affect systems-level auditory function. In particular, we describe a novel function of nicotinic acetylcholine receptors to regulate glutamate synapses containing N-methyl-D-aspartate receptors during early postnatal development. The transient regulation of developing glutamate synapses also defines a window of vulnerability during which exposure to exogenous nicotine disrupts synapse development. Thus, it appears that nicotinic regulation of glutamate synapses is a critical feature of auditory cortex development.     

CXCR4和CXCR7在甲状腺癌中的表达及病理意义

研究甲状腺癌组织中趋化因子4受体（CXCR4）和趋化因子7受体（CXCR7）的表达情况及临床病理意义。应用免疫组织化学PV-6000法及Westernblot法检测CXCR4与CXCR7在甲状腺癌中的表达。二者在甲状腺癌与甲状腺良性疾病组织的差异均具有统计学意义（P〈0．05）,在甲状腺癌中表达仅与淋巴结转移有关（P〈0．05）,CXCR4与CXCR7之间呈正相关。Westernblot结果提示二者在甲状腺癌中的表达率高于癌旁及甲状腺腺瘤。CXCR4和CXCR7的表达水平与淋巴结转移相关,可作为甲状腺癌预后的判断指标。     

非小细胞肺癌 EG FR 基因突变检测与临床意义

采用荧光PCR法对199例晚期非小细胞肺癌（NSCLC ）组织进行表皮生长因子受体（EGFR ）基因突变检测,分析EGFR基因突变的分布特征及其与临床病理特征的相关性。结果显示56例（28．1％）存在EGFR基因突变,其中27例（13．6％）为外显子19突变,25例（12．6％）为外显子21突变,2例为外显子18突变,1例外显子20突变,1例外显子18和20的共突变。另外,除广东及安徽省铜陵市外,辽宁地区NSCLC患者EGFR基因突变率及主要突变类型与其他地区相符,常见于外显子19、21突变,其中腺癌、不吸烟患者突变率更高,更适宜EGFR-TKI靶向治疗。     

EGFR突变NSCLC二线TKIs治疗优化选择

恶性肿瘤的治疗已经进入驱动基因指导下的个体治疗时代,肺癌患者应该进行多基因检测,特别是表皮生长因子受体（EGFR）基因突变。EGFR基因突变的非小细胞肺癌（NSCLC）患者,如果一线接受了化疗,二线应该选择表皮生长因子受体一酪氨酸酶抑制剂（EGFR—TKIs）。EGFR基因突变的NSCLC患者一线EGFR—TKIs治疗失败后,二线治疗应该是个体化合理选择,包括局部放疗、化疗和继续EGFR—TKIs。目前一代和二代EGFR—TKIs药物之间未见到显著疗效差别。第三代EGFR—TKIs是目前的EGFR—TKIs耐药后的最有希望的选择,特别是针对T790M突变耐药。     

环境雌激素双酚A对成年小鼠学习记忆和突触结构的影响*

双酚A (bisphenol, BPA)是一种广泛存在的环境内分泌干扰物,它可与雌激素受体结合干扰内源性雌激素对中枢神经系统的调控作用。本研究通过将10周龄小鼠灌胃染毒BPA (0.4、4、40 mg/kg/day)3个月,研究长期BPA暴露对成年小鼠记忆行为和突触可塑性的影响。开场行为测试结果表明, BPA (0.4、4、40 mg/kg/day)增加雄性的站立次数和理毛频率, BPA (4 mg/kg/day)却显著减少雌鼠的站立次数。水迷宫和被动回避行为模型检测显示, BPA主要损伤雄鼠的空间学习记忆和被动回避记忆。通过制备海马CA1区超薄切片后,电镜观测发现, BPA (0.4、40 mg/kg/day)暴露降低雄鼠海马CA1区突触数密度,缩短雄鼠突触前活性带长度,减小雄鼠突触后致密体(PSD)厚度,增加雄鼠突触间隙宽度。进一步用Western blot方法检测突触前、后的标志性蛋白Synapsin I和PSD95以及兴奋性氨基酸NMDA受体NR1亚基和AMPA受体GluR1亚基蛋白的表达,发现BPA暴露致雄鼠Synapsin I、PSD95、NR1蛋白表达水平下调。而BPA对雌鼠的记忆行为、突触形态、突触蛋白和受体蛋白均没有明显作用。以上结果提示长期B PA暴露性别特异性地影响成年小鼠的活动性和探究行为,损伤雄鼠的学习记忆,这些作用可能通过下调突触蛋白和NMDA受体的表达而负性影响突触结构可塑性,最终影响雄鼠的学习记忆功能。     

A meta‐analysis of serotonin metabolite 5‐HIAA and antisocial behavior

During the past 25 years, researchers have examined the relationship between neurochemical variables and antisocial behavior in human adults, but none has been studied more intensely than the serotonin metabolite 5‐hydroxyindoleacetic acid (5‐HIAA). The goal of the current study was to employ meta‐analytic procedures to quantitatively evaluate selected evidence on the relationship between 5‐HIAA and antisocial behavior. It was expected that antisocial groups would show reduced cerebrospinal fluid 5‐HIAA compared with non–antisocial groups. This study also aimed to assess moderators that could influence the relationship between 5‐HIAA and antisociality. An electronic search and strict inclusion criteria identified 20 reports used in this meta‐analysis. Results showed a significant overall mean effect size (ES = –.45, P < .05) in the direction of lowered 5‐HIAA in antisocial vs. non–antisocial groups. A significant moderating effect for age indicated that groups comprised of antisocial individuals younger than 30 years exhibited larger negative effect sizes (ES = –1.37, P < .05) than groups with older subjects (ES = –.31, P < .05). There were no moderating effects for gender, target of violence, history of suicide, and alcoholism. Age effects may help explain age‐related declines in crime. The fact that effects did not differ based on other moderating variables supports models of reduced serotonin in antisocial individuals, regardless of type of crime or psychiatric problems. Aggr. Behav. 28:299–316, 2002. © 2002 Wiley‐Liss, Inc.     

Effect of treatments for depression on quality of life: a meta-analysis*

Cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) are the two first-line treatments for depression, but little is known about their effects on quality of life (QOL). A meta-analysis was conducted to examine changes in QOL in adults with major depressive disorder who received CBT (24 studies examining 1969 patients) or SSRI treatment (13 studies examining 4286 patients) for their depression. Moderate improvements in QOL from pre to post-treatment were observed in both CBT (Hedges’ g = .63) and SSRI (Hedges’ g = .79) treatments. The effect size remained stable over the course of the follow-up period for CBT. No data were available to examine follow-ups in the SSRI group. QOL effect sizes decreased linearly with publication year, and greater improvements in depression were significantly associated with greater improvements in QOL for CBT, but not for SSRIs. CBT and SSRIs for depression were both associated with moderate improvements in QOL, but are possibly caused by different mechanisms.     

Because difficulty is not the same for everyone: the impact of complexity in working memory is associated with cannabinoid 1 receptor genetic variation in young adults

Individual differences in working memory ability are mainly revealed when a demanding challenge is imposed. Here, we have associated cannabinoid 1 (CB1) receptor genetic variation rs2180619 (AA, AG, GG), which is located in a potential CNR1 regulatory sequence, with performance in working memory. Two-hundred and nine Mexican-mestizo healthy young participants (89 women, 120 men, mean age: 23.26 years, SD?=?2.85) were challenged to solve a medium (2-back) vs. a high (3-back) difficulty N-back tasks. All subjects responded as expected, performance was better with the medium than the high demand task version, but no differences were found among genotypes while performing each working memory (WM) task. However, the cost of the level of complexity in N-back paradigm was double for GG subjects than for AA subjects. It is noteworthy that an additive-dosage allele relation was found for G allele in terms of cost of level of complexity. These genetic variation results support that the endocannabinoid system, evaluated by rs2180619 polymorphism, is involved in WM ability in humans.