Role of the striatal cholinergic system in the regulation of learned manipulation in rats

The experiments were performed on adult Wistar male rats trained to push with the forepaw on a fixed piston inside a narrow tube. It was found that after localized intracerebral injection of a cholinergic antagonist into the dorso-lateral (but not medial) neostriatum (i.e., the caudato-putamen) the behavioral performance requiring brief innate movements remained unchanged, but the performance requiring a prolonged pushing movement (> 50 msec) became disrupted. Microinjection of carbacholine (0.03-3 μ g/1 μ1) did not affect the performance of the acquired movements, whereas scopolamine (3 μ g/1 μ1) led to the significant decrease in pushing time. We conclude that changes in the state of the dorso-lateral neostriatal cholinergic system result only in disturbances of the sensory-controlled component of a complex instrumental movement. The 1994 Pavlovian Society Young Investigator Awardee was Nadezda Dubrovskaya, first author of this paper, which was presented at the annual meeting of the Pavlovian Society, July 3, 1994, in Prague, Czech Republic.     

Deficit in selective and divided attention associated with cholinergic basal forebrain immunotoxic lesion produced by 192-saporin; motoric/sensory deficit associated with Purkinje cell immunotoxic lesion produced by OX7-saporin

The immunotoxin 192-saporin, infused intracerebroventricularly into rats, destroys cholinergic neurons in the basal forebrain nuclei. Doses required for complete cholinergic loss also kill some Purkinje cells. The immunotoxin OX7-saporin, when infused intraventricularly into rats, destroys Purkinje cells in a pattern similar to that produced by 192-saporin, without affecting cholinergic neurons. Thus, we used OX7-saporin to distinguish behavioral effects of 192-saporin due to cerebellar damage versus those due to cholinergic cell loss. Three doses of 192-saporin (1.6, 2.6, and 3.3 micrograms/rat) were chosen along with a dose of OX7-saporin (2.0 micrograms/rat) that produced Purkinje loss equivalent to the two highest doses of 192-saporin. Groups of Fischer-344 rats were trained in the multiple choice reaction time task and retested with more complex tasks after lesioning. They were also tested in the water maze, passive avoidance, acoustic startle, and open field. The OX7-saporin group exhibited changes in many tests suggesting hypermotility and sensory deficits. The 192-saporin groups differed from the OX7-saporin group when they displayed deficits in multiple choice reaction time tasks in which novel challenges were introduced, including sessions with a noise distractor, shortened and lengthened intertrial intervals, and use of nine instead of five sources of light stimulus. The 192-saporin groups showed no impairment in the other tasks. The cholinergic basal forebrain lesion may mask some of the effects of cerebellar damage up to a threshold after which effects of Purkinje cell loss predominate when 192-saporin is administered intraventricularly.     

Individual Differences in Spatial Memory and Striatal ChAT Activity among Young and Aged Rats

Individual differences in spatial memory among young and aged rats were assessed using memory tasks related to integrity of the hippocampus and the neostriatum. Relationships were then examined between measures of spatial memory and regional choline acetyltransferase (ChAT) activity, a marker for cholinergic integrity. Twenty-four-month-old Long-Evans rats were impaired in comparisons with 6-month-old rats on measures of place learning, working memory, reference memory, and perseveration in water-maze tasks. Aged rats that were impaired on one measure of memory, however, were not necessarily impaired on other measures. ChAT activity in the ventromedial and dorsolateral neostriatum of aged rats was significantly reduced in comparisons with young rats whereas no difference was found in the hippocampus. Aged rats with the most ChAT activity in the anterior ventromedial neostriatum performed best on the place-learning and reference memory tasks but also made the most perseverative errors on the working memory task. In addition, young and aged rats with the most ChAT activity in the anterior dorsolateral neostriatum were those with the least accurate working memory. No relationships were found between ChAT activity in the hippocampus and spatial memory. Thus age-related memory impairment has components that can be segregated by measuring relationships between cholinergic integrity in subregions of the anterior neostriatum and memory tasks with different strategic requirements.     

干预胆碱M受体对药物成瘾的影响及其与多巴胺的关系

药物成瘾是一类精神及行为障碍, 涉及到中枢神经系统的病变。毒蕈碱受体(Muscarinic receptor, M受体)属于胆碱能受体, 分5种亚型。行为学研究表明, 干预M受体能有效影响药物成瘾行为, 但其神经机制还亟待探索。阿片类药物与精神活性药物均能激活中枢多巴胺系统, 而M受体与多巴胺系统在多个脑区产生了交互作用。其中激动M2及M4受体抑制了多巴胺系统功能, 而激动M5受体增强了多巴胺系统功能, 与干预M2、M4、M5受体对药物成瘾行为的影响相对应。以上证据提示, 干预M受体可能通过影响多巴胺系统对药物成瘾起作用。     

中枢胆碱能系统对吗啡成瘾的影响研究现状

介绍了中枢胆碱能系统对吗啡成瘾的影响及其机制。研究结果表明,吗啡成瘾过程中伏隔核等脑区细胞间乙酰胆碱水平发生了改变;去除伏隔核等脑区胆碱能细胞强化了吗啡成瘾行为;胆碱能激动剂和抑制剂都能干预吗啡成瘾、但机制可能不同——前者可能通过与多巴胺能交互作用来实现,后者可能通过干扰记忆或者加速吗啡代谢而发挥作用;胆碱能受体对吗啡成瘾也具有重要影响     

Amygdaloid function in the central cholinergic mediation of shock-induced aggression in the rat

A series of experiments was designed to examine the role of central cholinergic mechanisms in shock-induced aggression. Cholinergic blockade in the basolateral amygdala, ventral hippocampus, or dorsal hippocampus resulted in greatly reduced levels of fighting in response to footshock. However, while pain sensitivity remained unaltered in the amygdala group, both of the hippocampal groups exhibited decreased shock sensitivity. Further investigation of the amygdala revealed (1) increased fighting in response to increased cholinergic levels, (2) neuroanatomical specificity to the basolateral division of this complex, (3) that an intact basolateral amygdala is essential to the normal manifestation of shock-induced aggression, and (4) that social attraction remains unaltered by cholinergic blockade of the basolateral amygdala. Motor coordination and motor activity were not significantly affected in any treatment condition.     

全身炎症反应综合征治疗新策略——胆碱能抗炎通路

全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)是各种原因刺激机体产生失控的全身性炎症反应的统称,严重者可致多器官功能障碍综合征。迷走神经及其递质乙酰胆碱所构成的胆碱能抗炎通路可以有效抑制局部和全身炎症反应。本文将从胆碱能抗炎通路的作用特点分析激活胆碱能抗炎通路对全身炎症反应综合征的潜在治疗前景。     

Directional interaction of midbrain and hypothalamus in the control of carbachol-induced aggression

Microinjection of carbachol into the ventromedial part of the anterior hypothalamus or the ventrolateral part of the mesencephalic central gray elicits affective aggression in the cat. Pretreatment with atropine in the same site blocks carbachol-induced aggression. Prior administration of atropine into the midbrain blocks aggression induced by carbachol injections into the hypothalamus, but atropine injected into the hypothalamus does not prevent affective aggression elicited by carbachol administered into the midbrain. The results demonstrate a directional interaction between midbrain and hypothalamus, and provide suggestive evidence for a hierarchal organization of these limbic structures in the control of cholinergically-mediated affective aggression.     

Increased regional cerebral glucose metabolism and semantic memory performance in Alzheimer's disease: A pilot double blind transdermal nicotine positron emission tomography study

Nicotinic receptor dysfunction and impaired semantic memory occur early in Alzheimer's disease patients (AD). Previous research implied that nicotine's ability to enhance alertness, arousal, and cognition in a number of nonclinical populations was a function of its ability to stimulate CNS nicotinic cholinergic receptors. In this study it was hypothesized that transdermal administration of nicotine would increase both regional cerebral glucose metabolism (rCMRglc) and semantic memory (as assessed by verbal fluency). Two mild AD and two elderly controls underwent positron emission tomography scanning during a double blind nicotinic agonist verbal fluency challenge procedure. rCMRglc increases occurred in both AD patients, but not controls. In the two AD patients, verbal fluency scores increased by an average of 17%. One elderly control's verbal fluency increased, and the other decreased. These findings suggest that nicotine's effect on metabolism and verbal fluency is due to its ability to stimulate the cholinergic system.