前额皮层肾上腺素能受体在工作记忆中的作用

前额皮层去甲肾上腺素能神经支配主要来自脑干蓝斑核。前额皮层存在不同类型的肾上腺素能受体。其中突触后α2及β2肾上腺素能受体的激活提高工作记忆;α1及β1肾上腺素能受体的激活损害工作记忆。不同受体是通过激活不同的信号通路发挥对工作记忆的调节作用。来自人类被试的研究结果与对动物的研究结果之间尚存在不一致。了解前额皮层不同肾上腺素受体的作用为开发治疗与前额皮层功能失调相关疾病的药物提供了新的方向。     

Enhanced proliferation of progenitor cells following long-term potentiation induction in the rat dentate gyrus

The dentate gyrus (DG) is among the few areas in the mammalian brain where production of new neurons continues in the adulthood. Although its functional significance is not completely understood, several lines of evidence suggest the role of DG neurogenesis in learning and memory. Considering that long-term potentiation (LTP) is a prime candidate for the process underlying hippocampal learning and memory, these results raise the possibility that LTP and neurogenesis are closely related. Here, we investigated whether or not LTP induction in the afferent pathway triggers enhanced proliferation of progenitor cells in the DG. LTP was induced by tetanic stimulation in perforant path-DG synapses in one hemisphere, and the number of newly generated progenitor (BrdU-labeled) cells in the DG was quantified. Compared with the control hemisphere (stimulated with low-frequency pulses), the LTP-induced hemisphere contained a significantly higher number of newly generated progenitor cells in the dorsal as well as ventral DG. When CPP, an NMDA receptor antagonist, was administered, tetanic stimulation neither induced LTP nor enhanced progenitor cell proliferation, indicating that NMDA receptor activation, rather than tetanic stimulation per se, is responsible for enhanced progenitor proliferation in the control animal. Our results show that tetanic stimulation of perforant path sufficient to induce LTP increases progenitor proliferation in adult DG in an NMDA receptor-dependent manner.     

Activation of nociceptin opioid peptide (NOP) receptor impairs contextual fear learning in mice through glutamatergic mechanisms

The present study investigated whether the selective nociceptin opioid peptide (NOP) receptor agonist, Ro64-6198, impairs acquisition of fear conditioning through glutamatergic mechanisms. Systemic administration of Ro64-6198 (0.3 and 1 mg/kg) or the non-competitive NMDA receptor antagonist, MK-801 (0.03 and 0.1 mg/kg) prior to conditioning severely impaired contextual but not cued fear learning in C57BL/6N mice. When administered together at sub-effective doses, Ro64-6198 (0.5 mg/kg) and MK-801 (0.05 mg/kg), synergistically impaired contextual fear learning, but left cued fear learning intact. We next used the immediate shock deficit paradigm (ISD) to examine the effects of Ro64-6198 and MK-801 on contextual memory formation in the absence of the foot-shock. As expected, naive mice that were shocked briefly after being placed in the training chamber displayed no contextual fear conditioning. This learning deficit was elevated by prior exposure of mice to the training context. Furthermore, administration of Ro64-6198 and MK-801, either separately at amnesic doses (1 mg/kg and 0.1 mg/kg, respectively) or concomitantly at sub-effective doses (0.5 mg/kg and 0.05 mg/kg, respectively) significantly reduced the facilitating effects of context preexposure. These findings demonstrate the existence of functional antagonism between NOP and NMDA receptors that predominantly contributes to modulation of conditioned fear learning which involves spatial-processing demands.     

海马NMDA受体经SP-NK1受体通路参与慢性应激诱发的抑郁样行为

为探讨海马N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid, NMDA)受体与P物质(Substance P, SP)及其神经激肽1 (neurokinin1, NK1)受体在慢性不可预见性温和应激(chronic unpredictable mild stress, CUMS) 中的作用及其关系, 通过建立CUMS动物模型, 大鼠海马微量注射给药, 测量大鼠体重, 并采用糖水偏爱测试、旷场实验和悬尾实验等方法对大鼠进行行为学检测, 运用高效液相色谱(HPLC)法分析大鼠海马组织中SP和谷氨酸(glutamate, Glu)的含量变化。结果显示, CUMS诱发大鼠表现出明显的抑郁样行为, 海马组织中SP和Glu水平显著增加; 海马注射NMDA, 大鼠表现出与CUMS/SAL组相似的抑郁样行为, 且海马组织中SP的含量比正常对照组显著增加; 微量注射NK1受体阻断剂CP-96345和/或NMDA受体阻断剂MK-801后, 大鼠抑郁样行为明显改善, 且MK-801使CUMS导致的大鼠海马P物质水平升高得到明显控制, 而CP-96345没有明显改变CUMS引起的海马Glu水平升高; CP-96345使NMDA引起的抑郁样行为得到极显著改善。以上结果表明, 慢性应激引起大鼠海马Glu过量释放, 通过激活NMDA受体, 促进P物质合成释放增加, 激活NK1受体, 是导致抑郁样行为发生的重要途径之一。     

Depression in early adolescence: Contributions from relational aggression and variation in the oxytocin receptor gene

Interpersonal stress arising from relational aggression (RA)—the intentional effort to harm others via rejection and exclusion—may increase risk for depression in youth. Biological vulnerabilities related to the hormone oxytocin, which affects social behavior and stress responses, may exacerbate this risk. In a community sample of 307 youth (52% female; age range = 10–14 years), we tested whether (1) the association between RA and subsequent depressive symptoms was mediated through social problems and (2) a single nucleotide polymorphism (rs53576) in the oxytocin receptor gene (OXTR) moderated this indirect association between RA and depression, where GG homozygotes are predicted to be more sensitive to the effects of social problems than A‐allele carriers. Youth‐reported RA and depressive symptoms were measured using a structured interview and a questionnaire, respectively. DNA was extracted from saliva collected with Oragene kits. Consistent with the interpersonal theory of depression, the association between relational aggression and subsequent depressive symptoms was mediated by social problems. This indirect effect was further moderated by rs53576 genotype, such that GG homozygotes showed a stronger mediation effect than A‐carriers. These results suggest that rs53576 variants confer vulnerability for depression within the context of interpersonal risk factors, such that youth with the GG genotype may be particularly sensitive to the social consequences resulting from RA.

     

Individual differences in positivity offset and negativity bias: Gender-specific associations with two serotonin receptor genes

Individual differences in the evaluation of affective stimuli, such as the positivity offset and negativity bias may have a biological basis. We tested whether two SNPs (HTR2A; 102T>C and HTR1A; 1019C>G) related to serotonin receptor function, a biological pathway associated with affective regulation, were differentially related to positivity offset and negativity bias for males and females. Participants were 109 cigarette smokers who rated a series of affective stimuli to assess reactions to positive and negative pictures. Gender × genotype interactions were found for both SNPs. Males with the 102T allele showed a greater positivity offset than males with the 102C allele. For females, in contrast, the 1019C allele was associated with a greater positivity offset than the 1019G allele, whereas the 102T allele was associated with a greater negativity bias than the 102C allele. Identifying how gender differences may moderate the effect of serotonin receptor genes on affective information processing may provide insight into their role in guiding behavior and regulating affect.     

褪黑素受体MT1在骨肉瘤中的表达及临床意义

采用免疫组化法检测MT1在40例骨肉瘤及20例骨软骨瘤组织中的表达。结果显示MT1在骨肉瘤中的表达率（70％）明显高于骨软骨瘤（35％）（P〈0．05）。MT1的表达与骨肉瘤的Enneking分期、复发和转移相关（P〈0．05）,而与性别、年龄、肿瘤体积、Dahlin＇s组织学分型无关（P〉0．05）。因此,MT1可作...     

The role of nucleus accumbens and dorsolateral striatal D2 receptors in active avoidance conditioning

The role of dopamine (DA) in rewarding motivated actions is well established but its role in learning how to avoid aversive events is still controversial. Here we tested the role of D2-like DA receptors in the nucleus accumbens (NAc) and the dorsolateral striatum (DLS) of rats in the learning and performance of conditioned avoidance responses (CAR). Adult male Wistar rats received systemic, intra-NAc or intra-DLS (pre- or post-training) administration of a D2-like receptor agonist (quinpirole) or antagonist ((−)sulpiride) and were given two sessions in the two-way active avoidance task. The main effects observed were: (i) sulpiride and lower (likely pre-synaptic) doses of quinpirole decreased the number of CARs and increased the number of escape failures; (ii) higher doses of quinpirole (likely post-synaptic) increased inter-trial crossings and failures; (iii) pre-training administration of sulpiride decreased the number of CARs in both training and test sessions when infused into the NAc, but this effect was observed only in the test session when it was infused into the DLS; (iv) post-training administration of sulpiride decreased CARs in the test session when infused into the NAc but not DLS. These findings suggest that activation of D2 receptors in the NAc is critical for fast adaptation to responding to unconditioned and conditioned aversive stimuli while activation of these receptors in the DLS is needed for a slower learning of how to respond to the same stimuli based on previous experiences.