耳鸣动物模型的建立及药物对大鼠耳鸣的影响

目的：建立耳鸣动物模型并测试药物对动物耳鸣的影响。方法：让动物形成耳内有声音存在是安全的、而耳内无声音感往往伴随着危险因素这样一个条件反射,当动物有耳鸣时把它也作为部分安全的信号,在行为中表现出来。用注射水杨酸钠的造成动物耳鸣,通过不同组别大鼠行为实验的结果判断动物耳鸣的存在与否及药物的作用。结果：大鼠注射水杨酸钠后有鸣产生,抗癫痫药Ｌａｍｏｔｒｉｇｉｎｅ不能有效地缓解耳鸣,补肾中药复方改善了水杨     

水杨酸模型大鼠听觉功能的检测及中药的作用

耳鸣是一种主观感觉 ,其产生机理不清楚 ,尚无反映耳鸣的临床客观指标 ,也没有确切满意的治疗耳鸣的方法。大剂量水杨酸 (ｓａｌｉｃｙｌａｔｅａｃｉｄ ,简称ＳＡ)能引起人和动物耳鸣已是公认的事实。行为实验结果表明 ,大鼠被注射ＳＡ后有耳鸣产生。本实验观察了ＳＡ模型动物畸变产物耳声发射 (ＤＰＯＡＥ)及脑干听诱发反应 (ＡＢＲ)的变化 ,并记录下丘外侧核神经元单位放电 ,探索动物耳鸣情况下听觉传导通路电生理指标的变化以及中药复方对大鼠耳鸣的预防作用。1　材料与方法(1)分组及实验设计　成年雄性有色大鼠 (ＬｏｎｇＥｖａｎｓ) ,…     

慢性动脉血压监测模型在惊恐条件反射中的应用

目的：探索一种新的、可靠的模型,用于惊恐条件反射的相关研究。方法：通过使用条件刺激(声音)和非条件刺激(足部电击)相结合的方法,可使动物对条件刺激产生惊恐反应。同时对动脉血压进行长期监测并测定利多卡因阻断杏仁基底外侧核群前后的血压变化。结果：该惊恐条件反射建立后(需经4d训练),单独给予动物条件刺激即可引起血压明显升高。我们将它作为条件反射已形成的标志。此时,用利多卡因阻断杏仁基底外侧核群的作用,单独给予动物条件刺激不再引起血压明显升高。结论：慢性动脉血压监测模型在惊恐条件反射的研究中是一种可靠的动物模型。     

人与动物条件反射异同浅议

在初中《生理卫生》第十章第四节“高级神经活动”的教学中,条件反射的内容既是重点,又是难点。特别是人与动物条件反射的异同更难辨清。几年来,我做了一些探索,略有点滴体会,愿以抛砖引玉。首先,要搞清楚条件反射是人和动物都具有的生理活动。但动物只能对具体的外界刺激(物体的形状,声音频率的高低,光线的强弱等。)发生反应,建立条件反射。就是说,在动物     

关于家鸽单眼条件反射的研究

本工作采用食物性运动条件反射的方法和将 GABA 直接注于大脑皮层表面的方法,对家鸽的单眼条件反射进行了研究。获得以下结果:(1)在家鸽单眼和双眼条件反射的建立速度没有显著差别。条件刺激与非条件刺激结合8—15次后出现条件反射,结合30—40次后条件反射趋向巩固。(2)在条件反射巩固初期,即条件刺激与非条件刺激结合约70次时,由光刺激一眼所建立的食物性条件反射能向另侧眼传递,唯刺激另侧眼所引起的反应较弱,潜伏期较长;在条件反射巩固后期,即条件刺激与非条件刺激结合约400次时,这种传递现象即不复存在。(3)将0.4%的 GABA 0.03毫升注于左侧大脑皮层表面,可引起右眼对光刺激的条件反射的抑制;而将同样剂量的 GABA 注于右侧大脑皮层时,并不引起该条件反射的显著变化。对节拍器声的条件反射,在大多数动物均未受影响,只在少数动物有减弱现象。在实验过程中以注射等容量的生理盐水作为对照,未曾发现条件反射的任何变化。根据上述实验结果可以认为,在家鸽由光刺激一侧眼所建立的条件反射有逐渐集中于一侧的趋势,条件反射在两眼间的传递现象随结合次数的增加而不出现。注射 GABA的实验结果说明,在家鸽单眼对光刺激的条件反射主要与对侧大脑半球有关,同时也指出了鸟类大脑皮层在实现条件反射活动中的可能意义。     

豚鼠齿状回颗粒细胞在追踪性眨眼条件反应巩固过程中的活动

海马在追踪性眨眼条件反应的巩固过程中发挥重要作用,但解剖学上与其紧密联系的齿状回在此过程中的作用尚不清楚. 实验拟观察齿状回颗粒细胞在追踪性眨眼条件反应巩固过程中的放电活动,阐明齿状回在此海马依赖任务中所发挥的作用. 条件反射组动物 (n=8) 首先接受 200 ms 声音条件刺激,间隔 600 ms 后,再被给予 200 ms 吹气非条件刺激,多次重复配对,建立追踪性眨眼条件反应. 对照组动物 (n=8) 接受非配对出现的上述两种刺激. 采用在体单细胞外记录技术,研究习得条件反应豚鼠的齿状回颗粒细胞在条件反应巩固过程中的放电活动. 结果显示:a. 通过 14 天的训练,条件反射组动物均建立了追踪性眨眼条件反应,而非配对组动物则没有建立该条件反应;b. 齿状回颗粒细胞在追踪性眨眼条件反应的巩固过程中表现出不同的活动模式,如在声音条件刺激、间隔期或吹气非条件刺激出现后活动的增强. 这些结果提示:齿状回可能参与巩固追踪性眨眼条件反应所需的神经环路,其颗粒细胞在追踪性眨眼条件反应巩固过程中可能编码不同的信息.     

慢性不可预见性应激对大鼠恐惧条件反射和躯体感觉诱发电位的影响

目的:探讨慢性不可预见性应激对大鼠恐惧条件反射以及体感诱发电位的影响并分析可能的神经电生理机制。方法:26只雄性SD大鼠(190~200 g)随机分成两组(n=13):对照组和模型组。用慢性不可预见性应激刺激模型组大鼠,用恐惧条件反射实验检测两组大鼠的恐惧反应,用躯体感觉诱发电位检测大鼠脑电活动。结果:与对照组相比,模型组大鼠在恐惧记忆阶段不动时间百分比减小(56.64%±13.78%vs69.72%±18.10%,P<0.05),躯体感觉诱发电位的第二个正向波(P2)潜伏期也明显缩短(70.54±10.13 msvs78.46±7.80 ms,P<0.05)。相关性分析显示大鼠恐惧条件反射的不动时间与躯体感觉诱发电位潜伏期存在正相关(r=0.507,P<0.05)。结论:慢性不可预见性应激抑制大鼠恐惧反应,并缩短体表感觉诱发电位的潜伏期,恐惧反应行为与体感诱发电位潜伏期存在正相关,提示大鼠恐惧反应与体表感觉诱发电位可能有共同的神经递质机制。     

两品系大鼠在经典条件反射和操作式条件反射中的行为学表现

目的探讨SD、Wistar两种品系大鼠在经典条件反射和操作式条件反射中行为学表现差异,为研究脑的高级功能建立稳定的条件反射动物模型提供实验动物选择依据。方法选择8周龄的正常SD和Wistar大鼠,分别进行奖赏训练、单次操作训练、连续多次操作训练三种检测模式,研究SD、Wistar大鼠学习记忆能力。结果奖赏训练中,SD大鼠的鼻触次数显著性增多(vs.Wistar,P0.05);单次操作训练中,与SD大鼠比较,Wistar大鼠的总踏板次数(LPs)、比率(c LP/LP)显著升高(P0.05),总鼻触次数(NPs)于第5天差异有显著性,踏板潜伏期明显降低(P0.05),踏板速率则显著性的升高(P0.05)。连续多次操作训练中,Wistar大鼠鼻触次数显著性升高(P0.05),踏板次数、奖赏次数均增多,反应准确率也高于SD大鼠,但组间差异无显著性(P0.05)。结论经典条件反射阶段SD大鼠对饮水盒的探索能力强,表现出对奖赏物质较强的兴趣;而在奖赏操作条件反射阶段Wistar大鼠的表现优于SD大鼠。     

奖励性操作式条件反射任务在大鼠学习记忆研究中的应用

目的将奖励性操作式条件反射方法应用于学习记忆研究。方法首次采用奖励性操作式条件反射方法,设置单次操作训练、连续多次操作训练、信号辨识与消退四种检测模式,研究Wistar大鼠和SHR大鼠学习记忆能力。结果奖赏训练中,SHR组鼻触次数显著增多（vs.Wistar＆Donepezil,P〈0.05）;单次操作训练中,三组动物对操作反应的获得无显著差异;连续多次操作学习任务中,SHR组错误操作次数增多（vs.Wistar,P〈0.05）,奖赏获得次数减少（vs.Donepezil,P〈0.001）,反应准确率显著降低（vs.Wistar＆Donepezil,P〈0.05）;信号辨识任务中SHR组错误反应次数显著增多（vs.Wistar＆Donepezil,P〈0.05）,而反应准确率降低,组间差异有显著性（vs.Wistar＆Donepezil,P〈0.05）;消退实验中,三组动物差异无显著性。神经递质检测发现,SHR组大鼠谷氨酸[（1.0639±0.07086）mg/g]、乙酰胆碱[（2.7760±0.2609）μg/g]与五羟色胺[（1.2200±0.1137）μg/g]含量均显著低于Wistar组大鼠（P〈0.05）,多奈哌齐组大鼠乙酰胆碱含量显著增加[（3.9344±0.2747）μg/g]（vs.Wistar,P〈0.05;vs.SHR,P〈0.001）。结论奖励性操作式条件反射方法可作为一种正性增强条件反射检测新方法应用于大鼠学习记忆研究。     

论儿童心理发展的复合性条件反射

巴甫洛夫关于动物高级神经活动“两个信号系统”的学说,使人们认识到儿童心理的发展是以其神经系统后天性条件反射的建立为标志的。但先天性条件反射在儿童心理发展过程中的地位和作用及其与后天性条件反射的关系却仍被忽视。通过分析儿童先天性条件反射的存在形式、形成机制和表达条件,从广义生态学的理论角度,发现其与后天性条件反射的关系：先天性条件反射是后天性条件反射建立的基础,后天性条件反射是先天性条件反射表达的条件,它们互为因果复合一体。儿童心理的发展是先天性条件反射和后天性条件反射综合作用、世代演替、不断累进的结果。据此,本研究把这两个不可分割的条件反射称为“复合性条件反射”。     

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.     

Effects of an extinguished CS on competition with another CS

Three experiments were conducted using a conditioned taste aversion procedure with rats to examine the effect of nonreinforced presentations of a conditioned stimulus (CS) on its ability to compete with a target stimulus for manifest conditioned responding. Two CSs (A and B) were presented in a serial compound and then paired with the unconditioned stimulus. CS A was first paired with the US and then presented without the US (i.e., extinction) prior to reinforced presentation of the AB compound. Experiment 1 showed that A was poor at competing with B for conditioned responding when given conditioning and extinction prior to reinforcement of AB relative to a group that received both A and B for the first time during compound conditioning. That is, an extinguished A stimulus allowed greater manifest acquisition to B. Experiment 2 found that extinction treatment produced a poor CR to the pretrained and extinguished CS itself following compound conditioning. Experiment 3 found that interposing a retention interval after extinction of A and prior to compound conditioning enhanced A's ability to compete with B. The results of these experiments are discussed with regard to different theories of extinction and associative competition.     

Both Central and Peripheral Auditory Systems Are Involved in Salicylate-Induced Tinnitus in Rats: A Behavioral Study

Objective

This study was designed to establish a low dose salicylate-induced tinnitus rat model and to investigate whether central or peripheral auditory system is involved in tinnitus.

Methods

Lick suppression ratio (R), lick count and lick latency of conditioned rats in salicylate group (120 mg/kg, intraperitoneally) and saline group were first compared. Bilateral auditory nerves were ablated in unconditioned rats and lick count and lick latency were compared before and after ablation. The ablation was then performed in conditioned rats and lick count and lick latency were compared between salicylate group and saline group and between ablated and unablated salicylate groups.

Results

Both the R value and the lick count in salicylate group were significantly higher than those in saline group and lick latency in salicylate group was significantly shorter than that in saline group. No significant changes were observed in lick count and lick latency before and after ablation. After ablation, lick count and lick latency in salicylate group were significantly higher and shorter respectively than those in saline group, but they were significantly lower and longer respectively than those in unablated salicylate group.

Conclusion

A low dose of salicylate (120 mg/kg) can induce tinnitus in rats and both central and peripheral auditory systems participate in the generation of salicylate-induced tinnitus.     

Relapse processes after the extinction of instrumental learning: renewal, resurgence, and reacquisition

It is widely recognized that extinction (the procedure in which a Pavlovian conditioned stimulus or an instrumental action is repeatedly presented without its reinforcer) weakens behavior without erasing the original learning. Most of the experiments that support this claim have focused on several "relapse" effects that occur after Pavlovian extinction, which collectively suggest that the original learning is saved through extinction. However, although such effects do occur after instrumental extinction, they have not been explored there in as much detail. This article reviews recent research in our laboratory that has investigated three relapse effects that occur after the extinction of instrumental (operant) learning. In renewal, responding returns after extinction when the behavior is tested in a different context; in resurgence, responding recovers when a second response that has been reinforced during extinction of the first is itself put on extinction; and in rapid reacquisition, extinguished responding returns rapidly when the response is reinforced again. The results provide new insights into extinction and relapse, and are consistent with principles that have been developed to explain extinction and relapse as they occur after Pavlovian conditioning. Extinction of instrumental learning, like Pavlovian learning, involves new learning that is relatively dependent on the context for expression.     

Extinction, relapse, and behavioral momentum

Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a discriminative stimulus depends upon the baseline rate or magnitude of reinforcement associated with that stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have shown that relapse of operant behavior in reinstatement, resurgence, and context renewal preparations also is a function of baseline stimulus-reinforcer relations. In this paper we present new data examining the role of baseline stimulus-reinforcer relations on resistance to extinction and relapse using a variety of baseline training conditions and relapse operations. Furthermore, we evaluate the adequacy of a behavioral momentum based model in accounting for the results. The model suggests that relapse occurs as a result of a decrease in the disruptive impact of extinction precipitated by a change in circumstances associated with extinction, and that the degree of relapse is a function of the pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across experiments, relative resistance to extinction and relapse were greater in the presence of stimuli associated with more favorable conditions of reinforcement and were positively related to one another. In addition, the model did a good job in accounting for these effects. Thus, behavioral momentum theory may provide a useful quantitative approach for characterizing how differential reinforcement conditions contribute to relapse of operant behavior.     

Neural-network simulations of two context-dependence phenomena

This paper describes simulations of two context-dependence phenomena in Pavlovian conditioning, using a neural-network model that draws on knowledge from neuroscience and makes no distinction between operant and respondent learning mechanisms. One phenomenon is context specificity or the context-shift effect, the decrease of conditioned responding (CR) when the conditioned stimulus (CS) is tested in a context different from the one in which it had been paired with the unconditioned stimulus (US). The other effect is renewal, the recovery of CR in the training context after extinction in another context. For specificity (simulation 1), two neural networks were first given 200 CS-US pairings in a context. Then, the CS was tested either in the training context or a new context. Output activations in the new context were substantially lower. For renewal (simulation 2), two networks were first given 200 CS-US pairings in a context, then 100 extinction trials in either the same context or a new one, and then tested back in the training context. Output activations during the test phase were substantially higher after extinction in a new context. The results are interpreted in terms of the dynamics of activations and weights.     

Pavlovian Conditioned Approach Training in Rats

Cues that are contingently paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the attribution of incentive salience, or the transformation of neutral stimuli into attractive, "wanted'' stimuli capable of motivating behavior. Pavlovian conditioned approach (PCA) develops after the response-independent presentation of a conditioned stimulus (CS; e.g., a lever) that predicts the delivery of an unconditioned stimulus (US; e.g., a food pellet) and can be used to measure incentive salience. During training, three patterns of conditioned responses (CRs) can develop: sign-tracking behavior (CS-directed CR), goal-tracking behavior (US-directed CR), and an intermediate response (both CRs). Sign-trackers attribute incentive salience to reward-related cues and are more vulnerable to cue-induced reinstatement of drug-seeking as well as other addiction-related behaviors, making PCA a potentially valuable procedure for studying addiction vulnerability. Here, we describe materials and methods used to elicit PCA behavior from rats as well as analyze and interpret PCA behavior in individual experiments.     

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear

Fear is maladaptive when it persists long after circumstances have become safe. It is therefore crucial to develop an approach that persistently prevents the return of fear. Pavlovian fear-conditioning paradigms are commonly employed to create a controlled, novel fear association in the laboratory. After pairing an innocuous stimulus (conditioned stimulus, CS) with an aversive outcome (unconditioned stimulus, US) we can elicit a fear response (conditioned response, or CR) by presenting just the stimulus alone^1,2 . Once fear is acquired, it can be diminished using extinction training, whereby the conditioned stimulus is repeatedly presented without the aversive outcome until fear is no longer expressed³. This inhibitory learning creates a new, safe representation for the CS, which competes for expression with the original fear memory⁴. Although extinction is effective at inhibiting fear, it is not permanent. Fear can spontaneously recover with the passage of time. Exposure to stress or returning to the context of initial learning can also cause fear to resurface^3,4.Our protocol addresses the transient nature of extinction by targeting the reconsolidation window to modify emotional memory in a more permanent manner. Ample evidence suggests that reactivating a consolidated memory returns it to a labile state, during which the memory is again susceptible to interference^5-9. This window of opportunity appears to open shortly after reactivation and close approximately 6hrs later^5,11,16, although this may vary depending on the strength and age of the memory¹⁵. By allowing new information to incorporate into the original memory trace, this memory may be updated as it reconsolidates^10,11. Studies involving non-human animals have successfully blocked the expression of fear memory by introducing pharmacological manipulations within the reconsolidation window, however, most agents used are either toxic to humans or show equivocal effects when used in human studies^12-14. Our protocol addresses these challenges by offering an effective, yet non-invasive, behavioral manipulation that is safe for humans.By prompting fear memory retrieval prior to extinction, we essentially trigger the reconsolidation process, allowing new safety information (i.e., extinction) to be incorporated while the fear memory is still susceptible to interference. A recent study employing this behavioral manipulation in rats has successfully blocked fear memory using these temporal parameters¹¹. Additional studies in humans have demonstrated that introducing new information after the retrieval of previously consolidated motor¹⁶, episodic¹⁷, or declarative¹⁸ memories leads to interference with the original memory trace¹⁴. We outline below a novel protocol used to block fear recovery in humans.     

A comparison of the effects of discriminative and Pavlovian inhibitors and excitors on instrumental responding

In two experiments, the effects of Pavlovian or discriminative conditioned inhibitors on operant responding were investigated in rats. Experiment 1 found that a Pavlovian conditioned inhibitor for food suppressed food-reinforced lever pressing more than a non-differentially trained control stimulus did. Experiment 2 demonstrated that an operant discriminative inhibitor produced greater suppression of lever pressing than a Pavlovian conditioned inhibitor. Experiment 2 also found that compounding an operant discriminative stimulus (SD) for food-reinforced responding with another SD for food-reinforced responding resulted in more additive summation than when an SD was compounded with a Pavlovian conditioned excitor for food. The results of these experiments support two-factor theories that postulate that incentive and response discriminative processes summate algebraically when the processes are inhibitory or excitatory.