Changes in succinic dehydrogenase activity in the central nervous system of mice during morphine dependence development, withdrawal and naloxone treatment

The possible role of succinic dehydrogenase (SD) in producing physical dependence to morphine by affecting tissue respiration was investigated in Swiss albino mice during the development of morphine tolerance through a period of addiction and naloxone withdrawal therapy. Tolerance and physical dependence were induced by injecting the mice with morphine sulfate subcutaneously at 8-hour intervals, increasing the dose from 10 mg/kg BW every 24 h for 15 days. The animals were considered to be addicted when they were able to tolerate an otherwise lethal dose of 150 mg/kg 3 times a day. Results indicated that succinic dehydrogenase was inhibited throughout the 15-day period of morphine administration and that this effect was greatest in tolerant animals. Increasing the dose and duration of treatment did not cause further decreases in enzyme activity; instead, after 15 days levels of enzyme activity increased in addicted animals compared with tolerant mice. Furthermore, morphine abstinence for 2 days, markedly increased the levels of SD activity, while 6 days of abstinence had little effect. Naloxone withdrawal at each stage was associated with increased SD activity, but the increase was significant only in tolerant mice.     

The control of cell number during central nervous system development in flies and mice

Growth is confined within a size that is normal for each species, revealing that somehow an organism 'knows' when this size has been reached. Within a species, growth is also variable, but despite this, proportion and structure are maintained. Perhaps, the key element in the control of size is the control of cell number. Here we review current knowledge on the mechanisms controlling cell number in the nervous system of vertebrates and flies. During growth, clonal expansion is confined, the number of progeny cells is balanced through the control of cell survival and cell proliferation and excess cells are eliminated by apoptosis. Simultaneously, organ architecture emerges and as neurons become active they also influence growth. The interactive control of cell number provides developmental plasticity to nervous system development. Many findings are common between flies and mice, other aspects have been studied more in one organism than the other and there are also aspects that are unique to either organism. Although cell number control has long been studied in the nervous system, analogous mechanisms are likely to operate during the growth of other organs and organisms.     

Regulation of proliferation during central nervous system development

The retina is one of the best-characterized regions of the central nervous system (CNS) and has served as a model for many of the principles that now form the foundation for CNS development. In the past several years, a number of advances have been made in our understanding of the coordination of proliferation and cell fate specification during retinal development. In this review, we will draw on findings from studies of the retina and highlight similarities and differences in other regions in the CNS, namely the cerebellum and cortex. We will present a framework in which to pose challenges and outstanding questions for future studies on the coordination of proliferation and cell fate specification in the developing CNS.     

慢性吗啡给予、戒断及再给药过程中大鼠海马感觉门控的动态变化

药物成瘾被认为是药物长期作用于脑而产生的一种慢性复吸性脑疾病,长期反复的药物（如吗啡）滥用会导致一系列严重后果,如药物依赖、药物耐受、强迫性药物寻求等。本实验利用条件化位置偏好（conditioned place preference,CPP）模型来检测大鼠对吗啡依赖和心理渴求等过程;采用双声刺激听觉诱发电位来研究大鼠在慢性吗啡给予、戒断以及再给药过程中海马感觉门控（N40）的动态变化。吗啡组大鼠注射吗啡（10mg／kg,i．p．）12d,经历第一次戒断12d,再次注射吗啡（2．5mg／kg,i．P．）1d,之后经历第二次戒断2d;对照组大鼠注射同体积生理盐水,其余实验条件与吗啡组相同。CPP实验表明,这种药物给予方法促使大鼠对吗啡产生药物依赖和心理渴求。双声刺激诱发电位实验表明,吗啡组大鼠在吗啡给予期间海马感觉门控受到损伤;第一次戒断期的第1～2天海马感觉门控能力减弱,第3天增强,第4～12天逐渐恢复到正常水平;再次给予吗啡后海马感觉门控能力与对照组相比显著降低,并且随后2d的戒断期内海马感觉门控能力也一直保持较低水平,表明再次给药使大鼠海马感觉门控对吗啡更加敏感化。结果提示,长期反复的吗啡给予及再给药干扰了海马的感觉门控能力,吗啡成瘾对大脑可能产生长期影响。     

Fluctuations of acetylcholinesterase in the mouse spinal cord and in vivo sodium effect during the development of morphine tolerance,dependence, and withdrawal

Tolerance to and physical dependence on morphine were produced and assessed in Swiss inbred albino mice by giving morphine sulphate (s.c.) three times a day for a period of 15 days in an increasing dose of 10 mg/kg every 24 hours. Physical dependence was assessed taking naloxone induced jumping as well as weight loss during normal withdrawal into consideration. The effect of sodium ions in the potency of naloxone in antagonizing morphine's effect was also analyzed. The spinal cord was assayed for acetylcholinesterase employing both biochemical and histochemical parameters. It was found that the amount of the enzyme increased with the development of tolerance but the amount decreased as the animals became physically dependent. However, the values were significantly above the control. Administration of naloxone brought about a sudden and significant fall in the level of the enzyme. Normal withdrawal too was characterized by a weak activity of the enzyme. It has been found that sodium ions can influence naloxone antagonism in an in vivo system.     

Changes in ribonuclease activity during development of the mosquito, Aedes aegypti

In the mosquito Aedes aegypti, quantitative and qualitative changes have been detected in ribonuclease activity during development. Ribonuclease activity is particularly high in extracts from larvae, relative to that in extracts from pupae or adults. Larval extract is enriched for a ribonuclease that is heat-labile, has an alkaline pH optimum, and is extremely sensitive to the divalent cation, manganese. Extract from adult females is enriched for a heat-stable component that has an acidic pH optimum and is more active at 56 than at 30 degrees C. Throughout the vitellogenic cycle, no major changes in ribonuclease activity were detected in fat body extracts.     

Formation and specification of neurons during the development of the leech central nervous system

In the leech embryo, neurogenesis takes place within the context of a stereotyped cell lineage. The prospective germ layers are formed during the early cleavage divisions by the reorganization and segregation of circumscribed domains within the cytoplasm of the fertilized egg. The majority of central neurons arise from the ectoderm, and central neuroblasts are distributed throughout both the length and width of each ectodermal hemisegment. Much of the segmental ganglion arises from medial neuroblasts, but there are also lateral ectodermal neuroblasts and mesodermal neuroblasts that migrate into the nascent ganglion from peripheral sites of origin. Some of these migratory cells are committed to neurogenesis prior to reaching their central destination. In addition, the leech embryo exhibits a secondary phase of neurogenesis that is restricted to the two sex segment ganglia. Secondary neurogenesis requires that a mitogenic or trophic signal be conveyed from the peripherally located male sex organ to a particular set of centrally located neuroblasts, apparently via already differentiated central neurons that innervate the sex organ. The differential specification of neuronal phenotypes within the leech central nervous system occurs in multiple steps. Some aspects of a neuron's identity are already specified at the time of its terminal cell division and would seem to involve the lineal inheritance of developmental commitments made by one of the neuron's progenitors. This lineage-based identity can then be modified by interactions between the postmitotic neuron and other neurons or non-neuronal target cells encountered during its terminal differentiation. © 1995 John Wiley & Sons, Inc.     

Effect of chronic administration of lithium chloride on the development of dopamine receptor sensitivity during morphine withdrawal in rats

The morphine withdrawal syndrome was studied in male Wistar rats. Spontaneous aggressiveness, enhanced apomorphine aggressiveness, lowered pain threshold and decreased dopamine turnover were observed after withdrawal of 10-day treatment with the increasing doses of morphine (30-300 mg/kg). These changes attested to the increased sensitivity of dopamine receptors. Administration of morphine in conjunction with lithium chloride in a dose of 2 mekv/kg prevented the development of dopamine receptor hypersensitivity. Also, this method did not produce the increased spontaneous and apomorphine aggressiveness or the decreased dopamine turnover. Meanwhile the pain threshold remained lowered.     

Cytokines in the central nervous system of mice during chronic relapsing experimental allergic encephalomyelitis

Clinical disease phases of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the Biozzi AB/H mouse model are associated with extensive cellular infiltration of the central nervous system, principally the spinal cord. The activation of these cells is further suggested by the immunocytochemical demonstration of cytokines (migration inhibition factor, interferon-gamma, tumour necrosis factor-alpha, and interleukins 1, 2, and 3) within these infiltrates. The in vitro functions attributed to these cytokines indicate their potential role in cell recruitment, activation, and differentiation of the ongoing immune response which could contribute to the pathogenesis of disease.     

The development of central nervous system control of the gill withdrawal reflex evoked by siphon stimulation in Aplysia

In older Aplysia, the central nervous system (CNS) (abdominal ganglion) exerts suppressive and facilitatory control over the peripheral nervous system (PNS) which initially mediates the gill withdrawal reflex and its subsequent habituation evoked by tactile stimulation of the siphon. In young animals, both the suppressive and facilitatory CNS control were found to be absent. In older animals, removal of branchial nerve (Br) input to the gill resulted in a significantly reduced reflex latency and, with ctenidial (Ct) and siphon (Sn) nerves intact, a significantly increased reflex amplitude and an inability of the reflex to habituate with repeated siphon stimulation. In young animals, removal of Br had no effect on reflex latency and with Ct and Sn intact, the reflex amplitude latency was not increased and the reflex habituated. Older animals can easily discriminate between different intensity stimuli applied to the siphon as evidenced by differences in reflex amplitude, rates of habituation, and evoked neural activity. On the other hand, young animals cannot discriminate well between different stimulus intensities. The lack of CNS control in young animals was found to be due to incompletely developed neural processes within the abdominal ganglion and not the PNS. The lack of CNS control in young Aplysia results in gill reflex behaviours being less adaptive in light of changing stimulus conditions, but may be of positive survival value in that the young will not habituate as easily. The fact that CNS control is present in older animals strengthens the idea that in any analysis of the underlying neural mechanisms of habituation the entire integrated CNS-PNS must be taken into account.     

NMDA受体与中枢神经系统发育

中枢神经系统兴奋性氨基酸离子型受体－ＮＭＤＡ受体,是由ＮＭＤＡＲ１和ＮＭＤＡＲ２两个亚单位共同构成的受体通道复合体。ＮＭＤＡ受本激活后可引起神经元细胞对Ｎａ＾＋,Ｋ＾＋和Ｃａ＾２＋通透性增强,产生兴奋性突触后电位,在中枢神经发育的过程中,ＮＭＤＡ受体通过不同亚型的选择性表达,改变自身的结构和功能,进而影响ＮＭＤＡ受体介导的Ｃａ＾２＋内流,调节神经元内Ｃａ＾２＋依赖的第二信使系统,最终实现对中枢神经     

中枢单胺类神经递质在酒精依赖中的分子作用机制

酒精依赖是以失去控制地饮用酒精为特征的慢性、复发性脑疾病, 业已成为严重的社会问题。中枢单胺类神经递质(包括多巴胺、5-羟色胺等)在酒精依赖症的发生、发展和系统功能失调中发挥着重要作用。文章探讨了单胺类神经递质关键调控点多巴胺受体、5-羟色胺受体、转运体、酪氨酸羟化酶、色氨酸羟化酶及单胺氧化酶基因等在酒精依赖中的作用机制, 结合本实验室在基因敲除小鼠模型方面的研究进展提出了酒精依赖分子机制的研究策略。在系统评述中枢单胺类神经递质介导的酒精依赖分子作用机制的基础上, 结合本实验室在酪氨酸羟化酶激活剂钙调蛋白依赖的蛋白激酶Ⅱ方面的研究成果探讨了可用于酒精依赖症治疗的作用靶点, 提出通过调整基因调控区的甲基化程度和改变pre-mRNA的选择性剪切等表观遗传学策略预防和治疗酒精依赖症, 同时根据基因多态性研究结果提出对酒精依赖症患者进行个性化预防和治疗的新策略。