Loss of cortical acetylcholine enhances amphetamine-induced locomotor activity
Loss of cortical acetylcholine enhances amphetamine-induced locomotor activity
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DOI：
10.1016/j.neuroscience.2004.05.038
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Olson, L
中科院分区：
文献类型：
--
作者：
Mattsson, A;Pernold, K;Olson, L
胆碱能障碍被认为与精神分裂症有关。在最近的一项研究中，我们发现脑室内(I.C.V.)免疫毒素192免疫球蛋白有效地破坏了从基底前脑到海马区和大脑皮质的胆碱能投射，显著促进了苯丙胺诱导的成年大鼠的运动活动。本实验的目的是评估隔-海马区和基底皮质胆碱能投射对苯丙胺高反应的贡献。192只注射免疫球蛋白的大鼠。从I.C.V.开始。192个免疫球蛋白的表达也破坏了小脑中的浦肯野神经元，这种细胞的丢失也需要被考虑在内。脑实质内分别向大细胞基底核和Broca内侧隔/斜角带注射192-Ig G-Saporin，选择性失神经支配大脑皮层和海马区。小脑浦肯野细胞选择性丢失是通过侧脑室注射实现的。OX7皂苷的交付。我们在运动活动笼中评估了这三种损伤对自发和苯丙胺诱导的运动活动的可能影响。我们发现，选择性地去皮质胆碱能神经，而不是去神经海马体或损伤小脑，可以引起类似于以前的侧脑室注射的多巴胺能高反应性。192次免疫球蛋白-皂苷试验。我们的数据与大脑皮质胆碱能神经传递障碍可能与精神分裂症的因果关系有关的假设是一致的。(C)2004年IBRO。爱思唯尔有限公司出版。保留所有权利。
Cholinergic disturbances have been implicated in schizophrenia. In a recent study we found that intracerebroventricular (i.c.v.) delivery of the immunotoxin 192 IgG-saporin, that effectively destroys cholinergic projections from the basal forebrain to hippocampus and cortex cerebri, leads to a marked facilitation of amphetamine-induced locomotor activity in adult rats. The aim of the present experiments was to evaluate the contribution of the septohippocampal versus the basalocortical cholinergic projections for the amphetamine hyper-response seen previously in i.c.v. 192 IgG-saporin injected rats. Since i.c.v. delivery of 192 IgG-saporin also destroys a population of Purkinje neurons in cerebellum, this cell loss needs to be taken into consideration as well. Cortex cerebri and hippocampus were selectively cholinergically denervated by intraparenchymal injections of 192 IgG-saporin into nucleus basalis magnocellularis and the medial septum/diagonal band of Broca, respectively. Selective loss of Purkinje cells in cerebellum was achieved by i.c.v. delivery of OX7 saporin. Possible effects of these three lesions on spontaneous and amphetamine-induced locomotor activity were assessed in locomotor activity cages.We find that selective cholinergic denervation of cortex cerebri, but not denervation of hippocampus or damage to cerebellum can elicit dopaminergic hyper-reactivity similar to that seen in previous i.c.v. 192 IgG-saporin experiments. Our data are compatible with the hypothesis that disturbances of cholinergic neurotransmission in cortex cerebri may be causally involved in forms of schizophrenia. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.