杏仁核c-fos的表达与条件反射性免疫抑制

以糖精水为条件刺激（conditioned stimulus,,CS）,免疫抑制剂-环磷酰胺为非条件刺激 （(unconditioned stimulus,,UCS),在两次CS-UCS结合训练后,观测不同时程再次单独呈现条件刺激对条件反射性免疫抑制和味觉厌恶性行为反应的变化以及大鼠杏仁核各亚核团内c-fos蛋白表达的影响。结果表明,条件反射性免疫抑制作用在训练后第5天较强,第30天基本消失,而味觉厌恶性条件反射始终稳定保持到第30天。条件反射组大鼠杏仁中央核c-fos蛋白表达在第5天非常密集,而第30天明显减少,与细胞免疫功能改变在时程和趋势上具有一致性。通过c-fos蛋白表达时程差异比较,提示杏仁中央核可能既与条件性的味觉厌恶性行为建立有关,也是参与介导CS诱导的免疫抑制效应的重要核团。     

条件反射性免疫抑制激活过程中下丘脑核团c-fos的表达

利用经典条件反射性免疫抑制的动物模型,以糖精水为条件刺激（CS）,免疫抑制剂-环磷酰胺为非条件刺激 （UCS）,观测两次CS-UCS结合训练后,再次条件刺激诱发条件反射性免疫抑制作用的动态改变,获得条件反射性免疫抑制和味觉厌恶性条件反射各自保持的情况,并在此基础上,采用c-fos免疫组化技术, 进一步观察再次条件刺激诱发条件反射性免疫抑制反应时大鼠下丘脑各核团内FOS蛋白的表达情况。结果表明,条件反射性免疫抑制作用在训练后第5天较强,第30天基本消失,而味觉厌恶性条件反射始终稳定保持到第30天。进一步研究显示出,下丘脑室旁核FOS蛋白表达在第5天非常密集,而第30天几乎没有表达,与细胞免疫功能改变在时程和趋势上具有一致性。通过FOS蛋白表达时程差异比较,提示下丘脑室旁核可能是CNS内介导CS诱导的免疫抑制效应的重要核团。     

味觉厌恶性条件反射建立后脑内c-Fos的表达

以新异味觉刺激糖精水的摄入为条件刺激,以腹腔注射环磷酰胺(CY,免疫抑制剂)或氯化锂(LiCl)为非条件刺激,分别使大鼠建立味觉厌恶性条件反射.在条件刺激日,糖精水在学习组大鼠下列脑区中诱发出密集的Fos表达下丘脑、杏仁核、边缘皮质等,而非学习组在这些区域中却没有或只有少量表达.另外,在丘脑前背侧核、扣带回、下丘脑外侧核、穹隆下器、压部后颗粒皮质、视上核,CY组的Fos表达明显多于LiCl组;而在伏核、杏仁基底外侧核、腹外侧隔核,LiCl组的Fos表达明显多于CY组,这种差异可能是两种药物的不同药理性质所致.     

动物信号追踪和目标追踪行为及其神经机制

信号追踪和目标追踪的实质是条件刺激和非条件刺激结合诱导的条件性接近反应.条件刺激的预测作用和诱因作用是信号追踪和目标追踪的重要机制;伏隔核、中央杏仁核和前扣带回在信号追踪和目标追踪过程中具有重要作用;然而,大脑皮层和海马损伤对两者影响较小.DA功能降低可损害信号追踪获得和表达;而脑内DA含量增加可提高目标追踪.未来的研究中,应该规范条件刺激和非条件刺激的类型和设置方法,针对不同的研究目的个别地或同时地测量信号追踪和目标追踪.     

催产素、孕激素和雌激素对厌恶的影响及其神经生理机制

厌恶是人和动物最基本的情绪之一, 起源于口腔对苦味(有毒)物质的排斥, 常伴有恶心呕吐和远离诱发刺激的强烈愿望, 具有回避潜在疾病威胁的功能。大量动物和人类研究表明, 催产素、孕激素和雌激素不同程度地影响核心厌恶刺激的感知、核心厌恶情绪的产生与表达、条件性厌恶习得和厌恶表情识别。三种激素主要通过作用于五羟色胺、γ-氨基丁酸、乙酰胆碱和谷氨酸等神经递质受体, 调节杏仁核、脑岛、前扣带回、壳核、梨状皮层、额中回等脑区活动, 影响厌恶加工。未来研究应当在准确测量激素水平和控制实验任务难度的基础上, 探究各激素对不同感觉通道厌恶加工的影响, 及其性别的调节作用; 同时结合脑成像技术和动物行为学, 明确各激素影响厌恶加工的神经内分泌机制。     

催产素对产后抑郁症患者母性行为的调节作用

产后抑郁症是指女性分娩后一段时间内出现的严重抑郁发作现象。研究表明, 催产素不仅参与分娩过程和正常的母性行为表达, 也在调节产后抑郁的发病及患者的母性行为中起到了重要的作用。产后抑郁症患者的情绪和认知功能受损, 这可能导致了母性行为表达质量的下降; 催产素可以通过中脑边缘多巴胺系统来调控母性行为, 作用于内侧视前区(MPOA)来激活中脑腹侧被盖区(VTA)-伏隔核(NAc)环路从而影响伏隔核内多巴胺的分泌; 催产素对产后抑郁症中母性行为的调节机制可能是通过调节五羟色胺系统的功能来发挥抗焦虑作用, 也可能是通过与其它激素的交互作用来加速母性行为的表达。未来研究进一步明确催产素在中枢神经环路中的功能差异, 以及社会支持对产后抑郁症患者催产素的使用带来的影响。     

MK-801与环境线索交互作用对吗啡行为敏感化的影响

为探讨MK-801与环境线索交互作用对吗啡诱导行为敏感化的影响,将42只大鼠随机分为对照组,MK-801组,吗啡组（匹配和非匹配）和MK-801+吗啡组（匹配和非匹配）。行为敏感化模型建立分为发展期,戒断期和表达期三个阶段。实验结果发现：同时给予MK-801（0.1mg·kg-1）会促进吗啡（5mg·kg-1）诱导大鼠行为敏感化的发展,而且会使MK-801成为大鼠行为敏感化表达所必需的条件性刺激。MK-801的内部线索作用过强,从而削弱了环境的外部线索作用。研究结果表明：MK-801对吗啡诱导行为敏感化的影响存在状态依赖（state-dependency）现象,提示在NMDA受体与行为敏感化关系的研究中应考虑选择刺激特性更小的药物     

情绪对内隐刻板印象表达的调节

采用IAT范式探讨不同情绪对内隐刻板印象表达的调节作用：实验1通过音乐唤醒被试的不同弥散性情绪状态(悲伤vs.愉悦), 并操纵其即时观念(刻板一致vs.刻板冲突), 探讨二者对内隐性别刻板印象表达的影响。实验2通过视频诱发被试不同的指向性情绪(同情vs.厌恶), 研究其如何调节大学生对不同感染途径的艾滋病患者和病毒携带者的内隐刻板印象表达。在此基础上引入四重模型(Quad Model)分析技术, 进一步细化情绪的调节作用究竟发生在认知加工的自动加工过程还是控制加工过程, 以及不同情绪是通过哪些心理成分调节内隐刻板印象的表达。结果表明：(1)当即时观念与刻板印象内容一致时, 积极弥散性情绪促进内隐刻板印象的表达; 反之则会抑制其表达; (2)弥散性情绪通过调节认知加工的自动化加工过程, 进而调节内隐刻板印象的表达, 但未参与调节控制性加工过程; (3)积极效价的指向性情绪会抑制被试对艾滋病患者的内隐刻板印象表达, 消极效价的指向性情绪会促进其表达; (4)指向性情绪通过自动激活成分, 调节内隐刻板印象表达的自动化加工过程; 同时也通过辨识力成分, 参与调节内隐刻板印象表达的控制性加工过程。     

面孔识别过程中多重社会亚范畴的交互作用

认知者往往依据陌生个体面孔所携带的性别、年龄、种族等多重社会范畴信息对其进行加工,以期快速识别和了解他人。在基于面孔识别的多重社会范畴加工过程中,亚范畴间存在着复杂的交互作用。研究者分别采用"Who Said What"范式、重复启动范式、加纳选择注意范式、鼠标追踪范式等方法,发现亚范畴间的内隐加工具有彼此削弱的特性,外显加工存在交互影响的不对称性和偏差性。动态交互理论对此进行了进一步的理论分析与阐释。今后需更加科学地区分社会范畴加工的各个阶段,凸显内隐和外显加工的区别与联系;同时进一步整合各研究范式,克服方法异质导致的结果偏差甚至矛盾。     

长期双酚A暴露对成年小鼠恐惧记忆的影响

双酚A (bisphenol, BPA)是一种广泛应用于塑料制品的环境内分泌干扰物, 具有弱雌激素和抗雄激素活性, 与雌激素受体有一定的亲和力。本实验探讨长期BPA暴露对成年小鼠恐惧记忆的影响及其神经机制。将9周龄雄性小鼠暴露于BPA (0.4、4、40 mg/kg/d) 90 d, 建立小鼠亚慢性BPA暴露模型后, 进行场景性条件恐惧训练, 然后分别在电击后1 hr及24 hr检测小鼠的僵立时间, 同时在电击前、电击后1 hr及24 hr检测海马相关蛋白表达变化。结果表明, BPA (4、40 mg/kg/d)暴露延长小鼠场景性条件恐惧训练后1 hr及24 hr的僵立时间。Western blot蛋白检测结果显示, 行为训练前, BPA降低了小鼠NMDA受体NR1亚基表达水平, 上调组蛋白去乙酰化酶2表达。行为训练后1 hr及24 hr, BPA促进海马NMDA受体亚基NR1和组蛋白H3乙酰化表达, 抑制组蛋白去乙酰化酶2表达, 同时促进ERK1/2磷酸化水平。以上结果表明, 长期BPA暴露提高成年小鼠恐惧记忆获得的同时延长恐惧记忆的保持; 该作用可能通过激活海马的ERK1/2通路而改变核内组蛋白乙酰化和NMDA受体水平进行。     

Taste Aversion Learning Based on Swimming and Lithium Chloride Injection in Rats: Implications From Cross-familiarization Tests and Stimulus Selectivity1

In rats, swimming causes avoidance of the taste solution consumed immediately before the swimming. Several lines of research have shown that this taste avoidance reflects Pavlovian conditioned aversion based on correlations between the taste and swimming-induced nausea. The present research compared swimming-based taste aversion learning (TAL) with conventional TAL based on nausea-inducing lithium chloride (LiCl). By exploiting cross-familiarization techniques, Experiments 1A and 1B suggested that different physiological states are induced by swimming and LiCl. This claim was supported by Experiment 2, which reports stimulus selectivity in saccharin and sucrose aversions based on swimming and LiCl.     

Rapid, Labile, and Protein Synthesis– Independent Short-Term Memory in Conditioned Taste Aversion

Short-term memory is a rapid, labile, and protein-synthesis-independent phase of memory. The existence of short-term memory in conditioned taste aversion (CTA) learning has not been demonstrated formally. To determine the earliest time at which a CTA is expressed, we measured intraoral intake of sucrose at 15 min, 1 hr, 6 hr, or 48 h after contingent pairing of an intraoral infusion of 5% sucrose (6.6 ml over 6 min) and toxic lithium chloride injection (76 mg/kg). Rats were implanted with intraoral catheters to allow presentation of taste solutions at arbitrary times. Intraoral intake was measured under conditions of long-delay, single-trial learning typical of CTA. Rats decreased intraoral intake of sucrose at 15 min after contingent pairing of sucrose and LiCl, but not after noncontingent LiCl or sucrose. Thus CTA learning can be expressed rapidly. To determine if short-term CTA memory is labile and decays in the absence of long-term memory, we measured intraoral intake of sucrose after pairing sucrose with low doses of LiCl. Rats received an intraoral infusion of 5% sucrose (6 ml/6 min); 30 min later LiCl was injected at three different doses (19, 38, or 76 mg/kg). A second intraoral infusion of sucrose was administered 15 min, 1 hr, 3 hr, 4.5 hr, 6 hr, or 48 hr later. The formation of long-term CTA memory was dependent on the dose of LiCl paired with sucrose during acquisition. Low doses of LiCl induced a CTA that decayed within 6 hr after pairing. Central administration of the protein synthesis inhibitor cycloheximide prior to LiCl injection blocked long-term CTA expression at 6 and 48 hr, but not short-term CTA expression at 1 hr. Thus, short-term memory for CTA learning exists that is acquired rapidly and independent of protein synthesis, but labile in the absence of long-term memory formation.     

A failure to find socially mediated taste aversion learning in Norway rats (R. norvegicus)

Observer rats interacted with conspecific demonstrators immediately after demonstrators ate a novel diet and were made ill by LiCl injection. Following their interaction with demonstrators, observers were tested for aversion to their ill demonstrator's diet. Previous research has shown that (a) an observer can extract information from a demonstrator sufficient to permit identification of the demonstrator's diet (Galef & Wigmore, 1983) and (b) a rat ill from LiCl toxicosis is an adequate unconditioned stimulus in a taste aversion learning paradigm (Lavin, Freise, & Coombes, 1980). Further, two of the present experiments demonstrated that cues emitted by a rat, reflecting the particular diet it has eaten, are an adequate conditional stimulus in a toxicosis-induced aversion learning situation. Observer avoidance of a diet previously ingested by an ill demonstrator was, however, not demonstrated. The implications of the failure to find socially mediated aversion learning are discussed.     

CAMKII inhibition in the parabrachial nuclei elicits conditioned taste aversion in rats

The conditioned taste aversion (CTA) paradigm was used to assess the role of Ca(2+)/calmodulin-dependent protein kinase (CAMKII) in associative learning. KN62, a specific inhibitor of CAMKII, was injected into the parabrachial nuclei (PBN) either immediately after saccharin drinking (CS) or after saccharin drinking and i.p. injection of LiCl (US). Injection of KN62 into the PBN after saccharin drinking elicited clear CTA (Exp. 1). This effect was dosage-dependent and site-specific (Exp. 2). The results are discussed in relation with an earlier report showing that CTA acquisition is disrupted by injection of Ca(2+)/phospholipid-dependent protein kinase (PKC) inhibitor chelerythrine into the PBN during CS-US interval. It is suggested that the principal serine/threonine kinases play different roles in CTA learning: whereas PKC activity is necessary for the gustatory short-term memory formation, CAMKII acts similarly to the US itself-an unexpected role of CAMKII in associative learning.     

Conditioned taste aversion is enhanced when the unconditioned stimulus is presented in a different context

Using a conditioned taste aversion procedure with rats as the subjects, two experiments examined the effect of presenting a conditioned stimulus (CS saccharin solution) in one context followed by an unconditioned stimulus (US LiCl) in a different context. Experiment 1 showed that animals which received the above-mentioned procedure (Group D) showed a more marked conditioned aversion to the CS than animals which were given both the CS and the US in the same context (Group S). Experiment 2 found that in both Group D and Group S, aversion to the CS increased when the subjects were exposed to the conditioned context after the conditioning. These findings supported the argument that the strength of the CS-US association acquired during conditioning is compared with that of the context-US to determine the magnitude of aversion revealed to the CS.     

Flavor preexposures in a conditioned taste aversion situation: a dissociation of behavioral and endocrine effects in rats

A series of experiments examined the effects of flavor preexposures on pituitary-adrenal/behavior relations in a conditioned taste aversion paradigm. It was found that reexposure to a novel milk solution paired earlier with lithium chloride (LiCl) elicited conditioned activation of the pituitary-adrenal system (Experiment 1). The unconditioned response to LiCl (measured by changes in plasma levels of corticosterone) did not vary as a function of prior (2 and 5 vs. 10) exposures to the milk solution (Experiment 2). Increased familiarity with the substance (resulting from 10 prior exposures) rendered the conditioning of a taste aversion to this substance less effective. Further, reexposure to this familiar substance after its pairing with LiCl was not accompanied by the characteristic conditioned pituitary-adrenal activation (Experiment 3). By titrating the number of conditioned stimulus (CS) preexposures (Experiment 4) it was found that within the range of preexposures manipulated (5-10), subjects exhibited (a) a coupling of behavioral and pituitary-adrenocortical responses when the conditioned taste aversion to the milk solution was paralleled by elevated plasma corticosterone (5-6 preexposures), (b) a coupling of these two response systems when flavor consumption was accompanied by suppressed plasma titers of corticoids (9-10 preexposures), or (c) a dissociation of the two system when the conditioned taste aversion was not accompanied by conditioned adrenocortical activity (7-8 preexposures). These data are discussed in terms of a dissociation in the effects of CS preexposures on conditioned adrenocortical and behavioral response systems.     

Conditioning Method Dramatically Alters the Role of Amygdala in Taste Aversion Learning

Although an important role for the amygdala in taste aversion learning has been suggested by work in a number of laboratories, results have been inconsistent and interpretations varied. The present series of studies reevaluated the role of the amygdala in taste aversion learning by examining the extent to which conditioning methods, testing methods and lesioning methods, influence whether amygdala lesions dramatically affect conditioned taste aversion (CTA) learning. Results indicated that when animals are conditioned with an intraoral (I/O) taste presentation, lesions of amygdala eliminate evidence of conditioning whether animals are tested intraorally or with a two-bottle solution presentation. Dramatic effects of amygdala lesions on CTA learning were seen whether lesions were made electrolytically or using an excitotoxin. In contrast, when animals were conditioned using bottle presentation of the taste, electrolytic lesions attenuated CTAs but did not eliminate them, and excitotoxic lesions had no effect. These results are consistent with the hypothesis that neural structures critical for CTA learning may differ depending on the extent to which the method of conditioned stimulus delivery incorporates a response component.     

Instrumental Outcome Devaluation Is Attenuated by the Anti-emetic Ondansetron

In three experiments we assessed the effect of an anti-emetic, the selective S-HT antagonist ondansetron, on (1) the conditioning of a taste aversion using lithium chloride (LiCl); (2) the expression of that aversion; and (3) instrumental outcome-devaluation effects. In Experiment 1 it was found that ondansetron reduced the aversion induced by LiCl when administered prior to the LiCl injection and also attenuated the expression of that aversion when administered prior to test sessions. In Experiments 2 and 3, thirsty rats were trained, in a single session, to lever press and chain pull for sucrose and saline solutions concurrently before being injected with LiCl. They were then re-exposed to both solutions, one after injection of vehicle and the other after injection of ondansetron. In a choice extinction test on the levers and chains, animals performed more of the action whose training outcome was re-exposed under ondansetron than the other action, whether the test was conducted after an injection of vehicle or after one of ondansetron.     

Microstructural analysis of ingestive behaviour reveals no contribution of palatability to the incomplete extinction of a conditioned taste aversion

An analysis of the microstructure of licking responses was used to investigate the effects of conditioning and extinguishing a taste aversion. Rats received a single pairing of 8% fructose with lithium chloride (LiCl) while controls received unpaired exposure to fructose and LiCl. Pairing fructose with LiCl produced a reduction both in consumption and in the size of licking clusters. Subsequent exposure to fructose in the absence of LiCl produced some extinction of the taste aversion although at asymptote there was a residual difference in consumption between the taste aversion group and unpaired controls. In contrast the reduction in lick cluster size did completely extinguish. Previous analyses of licking microstructure indicate that lick cluster size is related to the palatability of the ingested solution. Thus these results indicate that although taste aversion learning initially reduces the palatability of the cue solution this reduction is not permanent. These results are discussed with reference to the possibility that preparatory behaviours are more resistant to extinction than are consummatory behaviours.     

Within-compound associations of taste and temperature

In two experiments, rats were given exposures to two solutions of different tastes (sucrose or sodium chloride) at two different temperatures (warm or cold). In Experiment 1, the rats were then given either one of the tastes at room temperature followed by LiCl injections, or distilled water at one of the temperatures followed by LiCl injections. Rats poisoned after drinking a taste were then given a choice between distilled water at the two temperatures, while those poisoned after drinking distilled water at a temperature were given a choice between the two flavors at room temperature. Rats drank less of the solution that contained the stimulus previously paired with the poisoned cue, demonstrating within-compound associations of tastes and temperatures. Experiment 2 found that tastes were better conditioned in a taste aversion procedure when the taste-temperature compound was the same during conditioning as during preexposure. This result is interpreted as evidence against a view of within-compound learning that treats the compound as a unitary stimulus.