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慢性给予苯丁胺后对成年大鼠大脑乙酰胆碱酯酶活性的抑制作用及行为分析。

Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

机构信息

Laboratório de Bioenergética, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, 88806-000, SC, Brazil.

出版信息

Metab Brain Dis. 2012 Dec;27(4):453-8. doi: 10.1007/s11011-012-9331-9. Epub 2012 Jul 27.

DOI:10.1007/s11011-012-9331-9
PMID:22832793
Abstract

Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats.

摘要

苯丁胺是一种安非他命类食欲抑制剂,它在体内迅速转化为安非他命。它能提高大脑中外周多巴胺的水平。乙酰胆碱酯酶是一种调节酶,参与胆碱能突触,可能间接调节多巴胺的释放。因此,我们研究了成年大鼠长期给予苯丁胺是否会改变其回避记忆的获得和保持以及乙酰胆碱酯酶的活性。成年雄性 Wistar 大鼠接受了反复(14 天)腹膜内注射载体或苯丁胺(6.25、12.5 或 25mg/kg 腹膜内注射)。为了进行行为评估,动物被进行了抑制性回避(IA)任务和连续多次步下抑制性回避(CMIA)。在额皮质、海马体、下丘脑和纹状体中测量了乙酰胆碱酯酶的活性。苯丁胺(6.25、12.5 和 25mg/kg)的给药不会导致大鼠短期和长期 IA 或 CMIA 保留记忆受损。此外,更长时间暴露于苯丁胺给药会降低大鼠额皮质和纹状体中的乙酰胆碱酯酶活性,但海马体和下丘脑未发生变化。总之,本研究表明,慢性苯丁胺给药会降低大鼠大脑中的乙酰胆碱酯酶活性。然而,更长时间暴露于苯丁胺不会导致大鼠短期和长期 IA 或 CMIA 保留记忆受损。

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Stressing hematopoiesis and immunity: an acetylcholinesterase window into nervous and immune system interactions.强调造血和免疫:乙酰胆碱酯酶揭示神经系统与免疫系统的相互作用。
Front Mol Neurosci. 2012 Mar 16;5:30. doi: 10.3389/fnmol.2012.00030. eCollection 2012.
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Effects of amphetamine on dopamine release in the rat nucleus accumbens shell region depend on cannabinoid CB1 receptor activation.安非他命对大鼠伏隔核壳区多巴胺释放的影响取决于大麻素 CB1 受体的激活。
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Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.芬特明急性和慢性给药对幼年和成年大鼠 DNA 损伤参数的影响。
Mol Cell Biochem. 2013 Aug;380(1-2):171-6. doi: 10.1007/s11010-013-1670-2. Epub 2013 May 1.
反复接触安非他命会破坏多巴胺能对杏仁核-前额叶回路的调节以及认知/情绪功能。
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Brain energy metabolism is activated after acute and chronic administration of fenproporex in young rats.在幼鼠中急性和慢性给予芬普雷司后,脑能量代谢被激活。
Int J Dev Neurosci. 2011 Dec;29(8):937-42. doi: 10.1016/j.ijdevneu.2011.06.007. Epub 2011 Jun 23.
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Obesity: pathophysiology and clinical management.肥胖症:病理生理学与临床管理
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Role of the dopamine transporter in the action of psychostimulants, nicotine, and other drugs of abuse.多巴胺转运体在精神兴奋剂、尼古丁及其他滥用药物作用中的角色。
CNS Neurol Disord Drug Targets. 2008 Nov;7(5):393-409. doi: 10.2174/187152708786927877.
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Could the quality of dietary fat, and not just its quantity, be related to risk of obesity?膳食脂肪的质量而非仅仅其数量,是否与肥胖风险有关?
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