Modulation of MK-801-elicited mouse popping behavior by galantamine is complex and dose-dependent
Modulation of MK-801-elicited mouse popping behavior by galantamine is complex and dose-dependent
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DOI：
10.1016/s0024-3205(03)00642-8
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发表时间：
2003-09-19
期刊：
影响因子：
6.1
通讯作者：
Mastropaolo, J
中科院分区：
文献类型：
--
作者：
Deutsch, SI;Rosse, RB;Mastropaolo, J
苯环利定（PCP）是一种NMDA受体介导的神经传递的非竞争性拮抗剂，在易感个体中沉淀精神分裂症样精神病的能力与NMDA受体功能低下的病理发生的假设是一致的。由于PCP引起的精神病在精神病理学的所有相关领域都与精神分裂症相似，研究人员试图表征NMDA受体功能低下的动物模型。MK-801（二唑西平）与PCP一样，与NMDA受体相关的电离层中相同的疏水通道区域结合，并已被证明能引起小鼠剧烈的不规则跳跃行为，称为“跳”。mk -801诱导的小鼠爆裂是一种NMDA受体功能低下的动物模型，已被用于筛选治疗精神分裂症的新候选化合物。最近，乙酰胆碱信号在0烟碱受体水平上的选择性转导异常在精神分裂症中被描述。精神分裂症中尼古丁胆碱能异常的存在激发了人们对尼古丁受体正变构调节的潜在治疗作用的兴趣。加兰他敏是一种具有两个有趣特性的化合物：抑制乙酰胆碱酯酶和对烟碱神经传递的正变构调节。从理论上讲，加兰他明有望提高乙酰胆碱促进烟碱受体通道打开和离子电导的效率或可能性。正如预期的那样，在目前的研究中，MK-801在小鼠中引起的弹出行为具有统计学意义（T(22) = 2.16, P < 0.05）。100mg /kg的剂量显著减弱了mk -801引起的爆裂。加兰他敏的浓度（T(22) = 2.24, P < 0.05）。数据表明，尼古丁干预可以影响完整小鼠NMDA受体介导的神经传递。(C) 2003年Elsevier Inc.出版
The ability of phencyclidine (PCP), a noncompetitive antagonist of NMDA receptor-mediated neurotransmission, to precipitate a schizophreniform psychosis in susceptible individuals is consistent with the hypothesized pathologic occurrence of NMDA receptor hypofunction in this disorder. Because the psychosis' caused by PCP resembles schizophrenia in all of the relevant domains of psychopathology, investigators have sought to characterize animal models of NMDA receptor hypofunction. MK-801 (dizocilpine) binds to the same hydrophobic channel domain in the NMDA receptor-associated ionophore as PCP, and has been shown to elicit intense irregular episodes of jumping behavior in mice, termed "popping." MK-801-elicited mouse popping is an animal model of NMDA receptor hypofunction that has been used to screen novel candidate compounds for the treatment of schizophrenia. Recently, a selective abnormality in the transduction of the acetylcholine signal at the level of the 0 nicotinic receptor has been described in schizophrenia. The existence of a nicotinic cholinergic abnormality in schizophrenia has stimulated interest in a potential therapeutic role for positive allosteric modulation of nicotinic receptors. Galantamine is a compound that possesses two interesting properties: inhibition of acetylcholinesterase and positive allosteric modulation of nicotinic neurotransmission. Theoretically, galantamine would be expected to increase the efficiency or likelihood that acetylcholine will promote channel opening and ionic conductance at nicotinic receptors. As expected, in the current investigation statistically significant popping behavior was elicited by MK-801 in mice (T(22) = 2.16, P < 0.05). This MK-801-elicited popping was significantly attenuated by 100 mg/kg. of galantamine (T(22) = 2.24, P < 0.05). The data show that nicotinic interventions can influence NMDA receptor-mediated neurotransmission in the intact mouse. (C) 2003 Published by Elsevier Inc.