Effect of Co-administration of Morphine and Cholinergic Antagonists on Y-maze Spatial Recognition Memory Retrieval and Locomotor Activity in Mice

吗啡和胆碱能系统的相互作用已在多项研究中提到,本实验想查明吗啡是否能和胆碱能拮抗剂、东莨菪碱以及阿托品共同作用对小鼠的Y迷宫空间识别记忆提取产生影响.采用测试前腹腔给药的方法,选用3种剂量的吗啡(5、1.5、0.5mg/kg),两种剂量的东莨菪碱(1、0.1mg/kg),以及两种剂量的阿托品(0.5、0.1mg/kg),剂量由高到低相配对作为联合给药的手段.其结果表明:1)0.5mg/kg低剂量吗啡与0.1 mg/kg低剂量的东莨菪碱,或与0.1 mg/kg低剂最的阿托品联合给药的小鼠,在记忆提取测试中, 空间探查行为(各臂停留时间百分比)对新异臂没有偏好,而新奇探索行为(各臂访问次数百分比)仍保持了对新异臂的偏好,而相应剂最药物单独给药的小鼠记忆提取均没有被损害;2)吗啡能和东莨菪碱相互作用使小鼠的活动性显著增强.暗示吗啡和胆碱能拮抗剂对小鼠空间记忆提取的破坏存在一定程度的相互作用.

Effect of adrenalectomy and corticosterone replacement on prepulse inhibition and locomotor activity in mice

1 Stress is a risk factor in psychiatric illnesses such as schizophrenia. The aim of the present study was to investigate the effect of different circulating levels of the adrenal steroid corticosterone (CORT) on locomotor hyperactivity and prepulse inhibition of acoustic startle, two behavioural animal models of aspects of schizophrenia. 2 Male C57BL/6J mice (n = 10 per group) were anaesthetised with isoflurane and sham-operated or adrenalectomised (ADX). ADX mice were implanted with 50 mg pellets consisting of 100% cholesterol, or 2, 10 or 50 mg of CORT mixed with cholesterol. CORT pellet implantation dose dependently increased plasma CORT levels 3 weeks after surgery. Starting 1 week after surgery, mice were tested for prepulse inhibition after injection of saline or 5 mg kg(-1) of haloperidol. 3 In intact mice and in mice implanted with 10 mg of CORT, haloperidol treatment significantly increased prepulse inhibition (average values from 38 - 42 to 52%). Similar results were observed when testing the mice for amphetamine-induced locomotor hyperactivity (5 mg kg(-1)). In contrast, there was no significant effect of haloperidol in mice implanted either with cholesterol or 2 or 50 mg of CORT. 4 These results in behavioural animal models of schizophrenia suggest an important role of the stress hormone CORT in modulating dopaminergic activity in this illness.

Locomotor activity rhythm in the Japanese eel Anguilla japonica elvers

Under artificial LD cycles (6, 12, 18 L), the elvers of Japanese eel, Anguilla japonica, showed a 24 h cycle of locomotor activity rhythm being most active at light transitions: the eels' activity rose to a primary peak after lights-off, followed by a quiescent period during which they buried into the shelters or lying motionlessly on sand for most of the time, and then reached a secondary peak before lights-on. Elvers could resynchronize their activity rhythm with a new photo cycle within 4 d. Moreover, their activity level at dark phase significantly increased as the light period was prolonged: higher activity levels during shorter dark period. However, the elvers did not display clearly the existence of a circadian rhythm under constant light or dark conditions. The timing of daily activity rhythm evidenced in the Japanese eels may occur through the action of the LD cycles with a weak participation of an endogenous circadian system. In all the LD cycles, over 99% of the activity occurred in the dark phase, indicating that the eels were always nocturnally active no matter what time of day it might be. Under 12 L conditions, the eels' activity level and the time outside sand were significantly elevated both at light and dark phases as temperature increased from 10 similar to 15 to 20 similar to 25 degrees C. The activity rhythm pattern (i.e., two peaks occurring around light transitions) did not apparently change among temperatures. However, in contrast with the primary activity peaks immediately after lights-off at 20 and 25 degrees C, the timing of the primary peaks at 10 and 15 degrees C showed a latency of a few hours following lights-off, indicating the inhibiting effect of low temperature on the eels' activity.

Observations on the nocturnal activity and feeding behavior of Anguilla japonica glass eels under laboratory conditions

Glass eels of the temperate anguillid species, Anguilla japonica, clearly showed a nocturnal activity rhythm under laboratory conditions. Light-dark cycle was a determinant factor affecting their photonegative behavior, nocturnal locomotor activity, and feeding behavior. Under natural light conditions, glass eels remained in shelters with little daytime feeding, but came out to forage during darkness. They moved and foraged actively in the following dark, and then their activity gradually declined possibly because of food satiation. They finally buried in the sand or stayed in tubes immediately after the lights came on. Under constant light, glass eels often came out of the shelters to forage in the lights but spent little time moving outside the shelters (e.g. swimming or crawling on the sand). Glass eels took shelter to avoid light and preferred tubes to sand for shelter possibly because tubes were much easier for them to take refuge in than sand. Feeding and locomotor activities of the glass eels were nocturnal and well synchronized. They appeared to depend on olfaction rather than vision to detect and capture prey in darkness. Feeding was the driving force for glass eels to come out of sand under constant light. However, in the dark, some glass eels swam or crept actively on sand even when they were fully fed. The lunar cycles of activity rhythms of glass eels that have been observed in some estuarine areas were not detected under these laboratory conditions.

1、蜜蜂嗅觉学习记忆应用基础研究 2、吗啡和胆碱能拮抗剂联合给药对小鼠Y迷宫空间记忆提取及活动性的影响

一、蜜蜂嗅觉学习记忆应用基础研究特殊气味的探测在刑侦工作中意义重大，常用的警犬探测和仪器分析都有其局限之处。蜜蜂嗅觉灵敏，且学习记忆能力突出，具有为刑侦工作所用的潜力。基于此，我们希望通过训练蜜蜂将其对糖水奖励的伸喙反应与指定气味建立条件反射的原理，配合适当的训练方法，达到利用蜜蜂探测危险气味的目的。在实验中，我们首先比较了不同喂养方式的蜜蜂在气味学习中的差别。由于低浓度气味无法直接使蜜蜂建立条件化，我们采用了逐渐降低气味浓度的方法，成功训练蜜蜂对低浓度(3.6×10-7) 醋酸气味建立了条件反射。结果如下： 1)自然放养与人工孵化两种不同喂养方式的蜜蜂，各两组，分别学习醋酸CS+/薄荷CS-，或柠檬CS+/薄荷CS-的气味配对。以“获得(CS+)，巩固(CS-/CS+ CS+/CS- CS-/CS+)，检测，干净空气假阳性检测”的顺序操作。结果显示自然放养蜜蜂对醋酸气味没有偏好（第一次给醋酸气味伸喙率：6%），学习醋酸气味能力较低（24小时后检测正确率：66%， n=25），相对应，该类蜜蜂对柠檬气味显示出明显偏好(第一次给柠檬气味伸喙率：41%，P< 0.01)，而学习效果（检测正确率：50%，n=20）与醋酸组相近(P>0.05)。人工孵化的蜜蜂对醋酸气味学习能力较自然放养蜜蜂大大提高（检测正确率：96%, n=32， P<0.01），同时对柠檬的学习结果（检测正确率：80%, n=32）也明显提高(0.01

VTA-NAc内orexin A在吗啡和性奖赏相关行为中作用的研究

There are a lot of differences in the neural mechanisms underlying between drug reward and natural reward despite the common neual basis. Undoubtedly, revealing the common and the different mechanisms underlying drug reward and natural reward will promote the development of research on drug addiction. Among diversified natural rewards, sex is often compared to drug because sexual reward has more similarities to drug. The mesolimbic dopamine system (VTA-NAc pathway) is a common pathway activated by natural reinforcers and addictive drugs, mediating reward, emotion and motivation under physiological conditions. The neuroadaptations taking place in the central nervous system including the mesolimbic dopamine system after repeatedly drug taking leads to persistent drug craving, Orexin, a neuropeptide produced in the lateral hypothalamus, plays an important role in reward-associated, motivated behaviors. Orexin neurons have extensive projections to the mesolimbic dopamine system. In order to further investigate the roles of orexin A in drug reward, this study examined the regulatory roles of orexin A in the VTA and NAcSh on drug reinforcement (acqusition of morphine CPP) and drug-seeking behavior (expression of morphine CPP). Moreover, the roles of orexin A on drug reward were compared with sexual reward. The main results are as follows: 1. The expression of morphine CPP was inhibited by intracerebroventricularly (i.c.v.) administered OX1R antagonist SB334867; 2. The male unconditioned sexual motivation was not affected by i.c.v. administered SB334867. However, i.c.v. given orexin A inhibited unconditioned sexual motivation in sexually high-motivated rats but did not affect sexual motivation in low-motivated rats; 3. The acquisition and expression of morphine CPP was inhibited by SB334867 microinjected into the VTA. SB334867 or orexin A injected into the NAcSh did not influence the acquisition of morphine CPP, but orexin A increased the locomotor activity in rats treated with morphine (3mg/kg); 4. SB334867 microinjected into the VTA did not affect male copulatory behavior, neither affect the acqusition of copulatory CPP; 5. The expression of copulatory CPP was associated with increased Fos protein expression in hypothalamic orexin A neurons, and SB334867 microinjected into the VTA inhibited expression of copulatory CPP. These results suggest that, (1) endogenous orexin A is not involved in male unconditioned sexual motivation, but involved in drug craving; (2) orexin A in the VTA instead of in the NAc is involved in drug reinforcement; (3) orexin A in the VTA is critical for drug-seeking behavior, but it is still unclear for the role of orexin A in the NAcSh; (4) in contrast to drug reinforcement, orexin A in the VTA is not involved in reinforcing effect of sexual reward. Orexin A plays a role both in drug-seeking behavior and in sexual reward-seeking behavior, but the different orexin A neuron populations may be responsible for the roles of orexin A in two types of reward. In a word, the differential roles of orexin A in drug and sexual reward are found in the present study, which provides some evidence for further research on the mechanisms of drug addiction.

影响吗啡动物行为效应的因素及其机制

Credible and stable animal behavioral models are necessary to research the mechanisms of addiction in vivo, especially to study the relationship between memory or stress and drug addiction, which has been one of the focuses in this field. So the object of this study was to observe the influences of several factors on the behavioral effects of morphine shown in the paradigms of conditioned place preference (CPP) and locomotor activity (LA), and to explore the effects of adrenalectomy on LA induced by morphine in rats. In addition, the cortexes of rats were examined, which were exposed to chronic administration of several doses of morphine with or without foot shock. Moreover, a new behavioral model was built to quantify the motivation of drug seeking. The results showed that CPP was more sensitive to low dose of morphine than to high dose. The period of experiment could be shortened by increasing the training times everyday, whereas in this way the dose of morphine should be low enough to avoid the impact between the near two exposures to morphine. Effects of chronic administration of morphine on LA in rats were dose- and time- dependent, which supplied evidence to choose parameters in other behavioral models. The results obtained by the simplified LA paradigm showed that hyperactivity of low dose of morphine following hypoactivity, and naloxone had no effects on LA but blocked the locomotion effects of morphine. Obvious effects of morphine on LA of rats might depend on a reasonable level of plasma corticosterone, which may determine individual vulnerability to drug addiction. Stress may also potentiate the vulnerability by aggravating damage to cortex of rats induced by drug dose-dependently, which is suggested by the results of histological examination. The result that frontal and temporal cortexes and hippocampus were injured suggests that there may be a close relationship between memory and drug addiction. It was showed that the new behavioral model on the basis of Morris water maze might be used to quantify the motivation of drug-craving.

Spontaneous activity was unaffected by ration size in Nile tilapia and gibel carp

Two growth trials using a range of ration sizes from starvation to maximum feeding suggested that linear relationships existed between specific growth rate and ration size for Nile tilapia and givel carp, Continuous measurement of activity showed that activity level, in terms of distance swum per day, was not affected significantly by ration size in both Nile tilapia and gibel carp. (C) 2001 The Fisheries Society of the British Isles.

Amplitude/frequency of spontaneous mEPSC correlates to the degree of long-term depression in the CA1 region of the hippocampal slice

Prior synaptic or cellular activity influences degree or threshold for subsequent induction of synaptic plasticity, a process known as metaplasticity. Thus, the continual synaptic activity, spontaneous miniature excitatory synaptic current (mEPSC) may correlate to the induction of long-teen depression (LTD). Here, we recorded whole-cell EPSC and mEPSC alternately in the Schaffer-CA1 synapses in brain slice of young rats, and found that this recording configuration affected neither EPSC nor mEPSC. Low frequency stimulation (LFS) induced variable magnitudes of LTD. Remarkably, larger magnitudes of LTD were significantly correlated to smaller amplitude/lower frequency of the basal mEPSC. Furthermore, under the conditions reduced amplitude/frequency of the basal mEPSC by exposure to behavioral stress immediately before slice preparation or low concentration of calcium in bath solution, the magnitudes of LTD were still inversely correlated to mEPSC amplitude/frequency. These new findings suggest that spontaneous mEPSC may reflect functional and/or structural aspects of the synapses, the synaptic history ongoing metaplasticity. (C) 2005 Elsevier B.V. All rights reserved.