基于“相关线索-自动化用药行为”联结的成瘾记忆消退

成瘾记忆消退致力于消除成瘾者相关线索与药物奖赏效应的联结,以达到消除心理渴求、戒断成瘾行为的目的,但其效果还十分有限。最近,大量的动物和人类实验研究发现:在相关线索下,成瘾者的激活脑区不仅包括中脑边缘皮层-背内侧纹状体,还延伸到感觉运动脑区-背外侧纹状体。这意味着成瘾记忆中存在相关线索与自动化(习惯性)用药行为的联结。所以,与成瘾相关的记忆可能包含两种不同的成分:一是与药物奖赏效应相关的情绪记忆,另一种是与用药动作、技能有关的动作记忆(程序记忆)。由于在成瘾阶段,药物奖赏效应对药物使用和复发的作用已经相对减少,因此,针对成瘾记忆的消退训练,以相关线索与自动化用药行为的联结为标靶,可能可以取得更好的效果,值得做进一步的深入探索。     

冲动性对吗啡诱导的条件性位置偏爱及行为敏感化的影响

许多研究显示, 冲动性与尼古丁、可卡因、海洛因等药物成瘾显著相关, 但它对吗啡成瘾的影响尚未见到报道。本实验考察冲动性对吗啡诱导的条件性位置偏爱及行为敏感化的影响。实验采用延迟奖赏模型将大鼠的冲动性区分为高、中、低三个水平, 每个水平设置吗啡处理组和盐水处理组。结果发现：动物对吗啡诱导的条件性位置偏爱的程度表现为低冲动组>中冲动组>高冲动组, 并且中、低冲动组动物形成了条件性位置偏爱而高冲动组没有形成这种偏爱; 在行为敏感化表达期, 与相应的盐水组比较, 高、中冲动组动物的吗啡运动激活效应显著, 而低冲动组没有达到显著水平。这些结果提示, 条件性位置偏爱任务中, 动物的冲动性越高, 吗啡的强化效应越低; 行为敏感化任务中, 动物的冲动性越高, 吗啡的运动激活效应越高。由此可见, 动物的冲动性对吗啡诱导的条件性位置偏爱及行为敏感化的影响存在差异。     

网络游戏成瘾与海洛因成瘾存在相同的神经机制吗?——基于MRI的证据

网游成瘾与海洛因成瘾具有许多相似的临床表现,但其神经机制是否相同还不得而知。综合近5年来的MRI研究发现,两类成瘾存在部分相同区域的脑结构和功能损害,且在成瘾线索诱发下二者的4个成瘾相关环路(认知控制环路、奖赏环路、动机环路和记忆-学习环路)均出现了广泛而增强的脑区激活反应。但海洛因成瘾的脑损害区域偏向更高级的认知控制环路和奖赏环路,损害范围也更广(4个环路的功能连通性均降低),而网游成瘾的脑损害主要发生在相对低级的记忆-学习环路和动机环路,损害范围也较窄(功能连通性降低只发生在认知控制和记忆-学习环路之间)。这些结果说明,两类成瘾行为的神经机制既有相同点,又有差异性。     

情绪障碍及其干预:心理表象的视角

心理表象在多种情绪障碍中均表现出病理性特点。研究者基于心理表象主要对创伤后应激障碍、抑郁心境、双相障碍情绪和社交焦虑进行了心理病理学解释,尤其关注闪回和过度概化记忆等两种典型症状,并且重视心理表象在情绪症状维持中的作用。概括而言,研究者强调记忆形成与提取过程的异常、认知与行为的保护性策略的负强化、对事件及自我的认知偏差等三类因素对情绪障碍的致病作用。目前,针对或运用心理表象的干预与训练方法包括减少消极表象、改变消极表象内容、提高积极表象能力、提高记忆的具体性等四类。未来应注重侵入性表象的功能分析以及相关的心理病理学模型研究,并拓展干预与训练研究。     

物质成瘾人群金钱奖赏加工的异常机制及可恢复性

长期的成瘾物质使用造成奖赏系统的变化是成瘾过程发展和维持的关键, 这种病理性变化反过来会对奖赏系统的调节功能产生不利的影响, 引起认知表现和日常功能方面的障碍。近年来大量的功能性核磁共振成像研究表明物质成瘾人群的金钱奖赏加工相关的腹侧纹状体及其它奖赏脑区激活存在异常。而奖赏加工相关的纹状体激活可以作为治疗效果的预测器和临床恢复的指标; 这种奖赏加工异常可以通过戒断有所恢复。今后的研究需要进一步补充奖赏加工的事件相关电位研究, 研究物质成瘾人群奖赏加工的特异性, 并增加对家庭物质依赖史个体的奖赏加工研究, 以及奖赏与执行功能的交互作用机制的研究。     

干预条件性恐惧记忆表达的相关影响因素分析

创伤后应激障碍是个体经历严重应激后形成的一种焦虑障碍, 对其治疗的关键是熄灭由创伤应激导致的条件性恐惧记忆。条件性恐惧的动物模型研究发现恐惧记忆一旦获得后就难以熄灭, 容易复发, 而这一点也是PTSD的关键临床症状表现之一。因此, 如何更好更持久地熄灭恐惧记忆, 是一个具有重要理论和临床意义的研究热点。本文围绕促进恐惧记忆的长久消退和破坏恐惧记忆的再巩固两方面的行为或药理干预及机制进行综述。针对本文所述的几种基础实验处理, 临床上可以研究治疗创伤后应激障碍的相应疗法。     

外在奖赏对陈述性记忆的影响

学习和记忆是个体赖以生存和发展的前提,如何取得好的学习和记忆效果是心理学和神经科学关注的重点。近年来,许多研究揭示奖赏可以促进记忆效果,奖赏对记忆的影响逐渐成为心理学和神经科学的热点研究课题。大脑的中脑多巴胺奖赏系统与海马记忆系统在结构和功能上均有关联。奖赏通过编码和巩固阶段以不同机制对记忆效果产生作用：在记忆编码阶段,奖赏会激活奖赏系统、注意控制系统,将更多认知资源分配给奖赏相关信息,从而促进奖赏信息的记忆效果;在记忆巩固阶段,奖赏会促进多巴胺释放,作用于海马对奖赏相关信息的加工,从而促进奖赏信息的记忆效果。未来研究可以关注奖赏对行为影响的复杂模式和内在奖赏对学习记忆的影响等方面。     

感知觉-运动系统在药物相关线索反应中的作用及神经机制

药物相关线索反应是成瘾行为的重要标志,它直接导致心理渴求和强迫性的刺激-反应式自动化用药行为。其神经机制是包含了经典和操作条件反射的联结学习。在联结过程中,除奖赏系统外,感觉-动作系统在相关线索反应中也起到了重要作用。其机理可能是与感觉运动脑区部分重合的镜像神经的理解、分析和推测动作意图目的以及内隐模仿的功能有关。另外,动作记忆的形成及功能也可能在这种自动化动作图式的形成中起到了重要的作用。其确切的机制需要进一步研究证据。     

药物成瘾者的感觉寻求人格特征

药物成瘾具有明显的心理成因,其中,成瘾者的人格特点,特别是感觉寻求人格特质,是导致药物成瘾的重要病原性因素。中脑边缘体多巴胺系统是感觉寻求行为与药物成瘾行为共同的脑奖赏系统,而多巴胺受体的遗传表达至少部分建立在个体执行新奇寻求和药物成瘾的行为上。感觉寻求特质对药物成瘾的作用受环境因素（父母,同伴）调节。文章也评述了感觉寻求相关研究所采用的测量工具。     

反馈负波及其近10年理论解释

个体决策后的反馈对随后的结果监控和行为调整起着至关重要的作用。事件相关脑电位研究发现, 反馈负波(feedback-related negativity, FRN)是与决策后反馈加工过程紧密相关的脑电成分。近10年来关于FRN的理论解释, 在最初经典的强化学习理论和情绪动机假说的基础上又提出了反应-结果的预测模型、奖赏正波理论以及积极情绪启动模型。未来的研究应该立足于大样本, 采用互补的研究手段和多样的分析技术来探讨FRN的心理意义; 同时考虑将FRN作为奖赏加工的脑电指标, 研究社会互动情境下的人类行为。     

The effects of prenatal stress on motivation in the rat pup

Exposure to prenatal stress (PNS) has been shown to induce a set of psychological and behavioral changes in developing offspring. We used the rodent model to investigate whether PNS produces changes in the ability of the pup to express social motivation. We used a set of behavioral tasks including monitoring ultrasonic vocalizations after isolation, a conditioned place preference, and a novel and familiar odor approach test. Pregnant Long-Evans rats were exposed to an unpredictable, variable stressor twice daily during the third week of gestation. Isolation vocalizations were assessed on postnatal day (PND) 10. Pup affinity for the dam was evaluated on PND 15. Typically, pups display a selective preference for an odor-paired environment only after the odor has been associated with the dam. This previous association produces a positive conditioned stimulus (CS). Normally, pups exposed to a neutral CS (odor paired with cotton balls) do not form this place preference. Results indicate that PNS exposed pups had significantly increased distress vocalizations and an equal preference for the positive and neutral conditioned stimuli. This type of alteration in forming early preferences could be detrimental because of decreases in the specificity of social learning and an impaired responsiveness in social relationships.     

Motivational processes and behavioral inhibition in breath holding

Large individual differences in breathing performance have made it difficult to investigate the effects of psychological variables on respiratory parameters. This study uses an experimental approach to investigating the effects of attentional and motivational factors on breath-holding span in humans. The effects of shock threat (negative incentive), monetary reward (positive incentive), and mantra meditation (attentional control) on breath-holding span at functional residual capacity (FRC) were compared. Based on Jeffrey Gray's (1975, 1987) theory of behavioral inhibition, it was predicted that shock threat would extend FRC breath holding. Breath holding was increased under the shock threat condition but not under the monetary reward or mantra meditation conditions.     

伏隔核和中脑腹侧被盖区内食欲素在吗啡奖赏中的作用

实验采用条件性位置偏爱（CPP）模型考察中脑腹侧被盖区（VTA）和伏隔核壳区（NAcSh）内食欲素（orexin）在吗啡奖赏中的作用。Wistar大鼠分为盐水训练组和吗啡训练组。3轮吗啡（或盐水）匹配训练前,双侧VTA或NAcSh内给予OXR1拮抗剂SB334867（VTA: 0, 1, 5μg;NAcSh: 0, 1, 3μg）;或2轮吗啡（或盐水）匹配训练前NAcSh内给予orexin A（0, 2, 4, 6μg）,观察其对吗啡CPP建立的影响。结果表明,VTA内给予SB334867抑制吗啡CPP建立,并存在剂量效应关系;NAcSh内给予SB334867或orexin A均未影响吗啡CPP建立,而orexin A可增加吗啡处理大鼠的运动性。以上结果表明,VTA和NAcSh内的orexin在吗啡奖赏中扮演的角色不同,可能调控成瘾行为的不同成分     

Orbital prefrontal cortex and guidance of instrumental behavior of rats by visuospatial stimuli predicting reward magnitude

The orbital prefrontal cortex (OPFC) is part of a circuitry mediating the perception of reward and the initiation of adaptive behavioral responses. We investigated whether the OPFC is involved in guidance of the speed of instrumental behavior by visuospatial stimuli predictive of different reward magnitudes. Unoperated rats, sham-lesioned rats, and rats with bilateral lesions of the OPFC by N-methyl-D-aspartate (NMDA) were trained in a visuospatial discrimination task. The task required a lever press on the illuminated lever of two available to obtain a food reward. Different reward magnitudes were permanently assigned to lever presses to respective sides of the operant chamber; that is, responses to one lever (e.g., the left one) were always rewarded with one pellet and responses to the other lever with five pellets. On each trial, the position of the illuminated lever was pseudorandomly determined in advance. Results revealed that OPFC lesions did not impair acquisition of the task, as the speed of conditioned responses was significantly shorter with expectancy of a high reward magnitude. In addition, during reversal, shift and reshift of lever position–reward magnitude contingencies and under extinction conditions, performance of the OPFC-lesioned and control groups did not differ. It is concluded that the OPFC in rats might not be critical for adapting behavioral responses to changes of stimulus–reward magnitude contingencies signaled by visuospatial cues.     

The hippocampal dentate gyrus is essential for generating contextual memories of fear and drug-induced reward

The hippocampus is believed to play a role in processing information relative to the context in which emotionally salient experiences occur but evidence on the specific contribution of the hippocampal dentate gyrus (DG) to these processes is limited. Here, we have used two classical behavioral paradigms to study the participation of the dorsal DG in context-conditioned reward and context-conditioned fear. Rats received intra-hippocampal vehicle or colchicine injections (4 microg/microl solution; 0.2 microl injections at 10 sites) that damaged the DG but spared other hippocampal subfields. In the first experiment, we used a place conditioning procedure pairing cocaine exposure (20 mg/kg, i.p.) with a specific context and vehicle treatment with another. While rats with sham lesions exhibited preference for the cocaine-paired context following conditioning, rats with lesions of the DG showed no evidence of cocaine-induced place preference. In the second experiment, rats with sham or colchicine lesions received a foot shock in a given context and conditioned freezing was measured upon reexposure to the shock-paired context (2, 24, 48 and 96 h after conditioning). Rats with sham lesions exhibited high levels of conditioned freezing when exposed to the conditioning context but rats with lesions of the DG showed impaired conditioning, behaving as controls that had experienced shock in a different context. These observations indicate that the integrity of the DG is essential for establishing a coherent representation of the context to which emotional experiences, either hedonic or aversive, are bound.     

Hippocampal associative cellular responses: dissociation with behavioral responses revealed by a transfer-of-control technique

Multiunit activity was recorded in the CA3 field of the dorsal hippocampus in freely moving rats during classical conditioning and subsequent presentation of the CS on operant baselines for food reward as well as shock avoidance. Rats were first trained in a nonsignaled bar-pressing-dependent shock omission task and in a food-motivated lever-pressing task (60-s VI). Five sessions with presentations of a previously habituated tone as a CS paired with footshock as a US were then given. Testing was carried out by presenting the CS alone while behavioral responses were maintained by reinforcement in both instrumental tasks on alternate sessions. As expected, the CS induced a marked suppression of lever pressing for food reward and a marked enhancement of bar-pressing for shock avoidance. The analysis of the frequency of multiunit discharges to the CS revealed that the hippocampal cellular responses established during classical conditioning were maintained while two different behavioral responses were exhibited to the CS. The results showed that the associative response of hippocampal neurons may be dissociated from the Pavlovian conditioned responses the CS elicits. They support the hypothesis that hippocampal cellular responses represent a neural index of the acquired CS-US associative representation.     

Circadian modulation of conditioned place avoidance in hamsters does not require the suprachiasmatic nucleus

Animals possess the ability to remember both the time of day as well as the location that noxious and potentially dangerous conditions occur. A behavioral expression of this learning is demonstrated in conditioned place avoidance (CPA). CPA is strongest when the time of testing matches the time of day that the prior training had occurred, suggesting the involvement of a circadian oscillator that modulates either memory retrieval or reactivity to the conditioned environment. In these experiments we show that time of day learning persists in the absence of the central circadian clock in the suprachiasmatic nucleus (SCN), demonstrating that memory for time of day is implicit in context conditioning and may involve a circadian oscillator that is distinct from the SCN.     

Behavioral specifications of reward-associated long-term memory enhancement in humans

Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the magnitude of reward, (3) the uncertainty of outcomes, and (4) the contextual availability of reward affect long-term memory. We show that episodic memory is enhanced only when rewards are specifically predicted by the semantic identity of the stimuli and changes nonlinearly with increasing reward magnitude. These effects are specific to reward and do not occur in relation to outcome uncertainty alone. These behavioral specifications are relevant for the functional interpretation of how reward-related activation of the SN/VTA, and more generally dopaminergic neuromodulation, contribute to long-term memory.     

心理神经免疫学研究

心理神经免疫学（Psychoneuroimmunology）是一门探索人类心身健康奥秘的新型边缘学科。它研究神经系统如何将心理因素转换为可以影响健康的生理状态的机制,特别是脑和行为如何影响免疫系统,又如何受到免疫系统的影响的。免疫系统和神经系统之间是否真正存在联系一直有争论,我们实验室围绕高级神经活动对免疫系统的作用开展了研究。工作包括：条件反射性免疫抑制和增强、情绪应激与免疫、心理行为干预与癌症等。这些工作不仅证实了心理调控,比如信号刺激、情绪和意念想象等,确实可以影响免疫系统的功能,而且对有关机制进行了探讨     

BAS Reward Responsiveness: A unique predictor of positive psychological functioning

Previous research on Reinforcement Sensitivity Theory has well-characterized the Behavioral Inhibition System in terms of its behavioral and emotional manifestations, but the Behavioral Approach System (BAS) is less well-defined, particularly regarding the prominence of reward sensitivity versus impulsivity. Furthermore, few researchers evaluate both systems in one model. We evaluated the relationship between Carver and White’s (1994) BIS/BAS Scales and areas of psychological functioning including internalizing, externalizing, affect regulation, and well-being. 497 undergraduates completed a battery of self-report measures. Two structural equation models indicate that the Reward Responsiveness subscale uniquely predicts adaptive functioning across all domains. Reward Responsiveness may be a more pure measure of BAS than other BAS traits and may be important for resilience from maladaptive psychological functioning.