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神经生物

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论坛首页  >  神经生物学讨论版   >  免疫染色
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【讨论】关于脑内给药剂量的问题

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楼主 goumi123
goumi123
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这个帖子发布于9年零131天前,其中的信息可能已发生改变或有所发展。
想研究药物脑内局部应用对动物行为的影响(已知该药通过干扰细胞内某信号通路发挥作用),目前知道细胞培养时的起效浓度,是否可以在脑局部也注射同样浓度?还有,如果知道静脉给药剂量或腹腔给药剂量,脑内局部给药剂量又该如何换算呢?希望有经验的战友介绍下。
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2010-08-06 16:29 浏览 : 1443 回复 : 3
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“目前知道细胞培养时的起效浓度,是否可以在脑局部也注射同样浓度?还有,如果知道静脉给药剂量或腹腔给药剂量,脑内局部给药剂量又该如何换算呢?希望有经验的战友介绍下。”

From my individual standpoint, I suppose, in many cases, there is no exact correlation between the dosages and ways of administration, that means the dosage, concentration or volume used in different ways may be quite different with each other. In addition, different organs, different animal strains, different genders, different ages, different time points may even have various applying dosages.

However, definitely, that does not mean all the drugs can not be converted each other among different ways of administration. At least, so far, I don't know yet (its not my field, we hope we can get some more details by some experts who have been involving in this area).

Therefore, when we don't exactly know the dosage of the drugs which will be used, I prefer to choose it which had been applied by the former experimenters in our lab or in the authoratively published articles. Even so, I just choose this as a reference or a guide to our own practical experience. Because sometimes things may not always the same since the time and people changed. So we need to do some short pre-experiments to confirm it, then we can use it undoubtedly in our own studies.

Below is a reference may be related with your topic or may not, you can choose it by your own justice. Hope this will give you some tips. Thanks for your time! Good luck!

Research
Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats
Pamela B Yang1,2 , Alan C Swann2 and Nachum Dafny1

1 Department of Neurobiology and Anatomy, The University of Texas-Medical School at Houston, P.O. Box 20708, Houston, Texas 77225, USA

2 Department of Psychiatry and Behavioral Sciences, The University of Texas-Medical School at Houston, P.O. Box 20708, Houston, Texas 77225, USA

Behavioral and Brain Functions 2006, 2:3doi:10.1186/1744-9081-2-3

The electronic version of this article is the complete one and can be found online at: http://www.behavioralandbrainfunctions.com/content/2/1/3

Received: 2 August 2005
Accepted: 17 January 2006
Published: 17 January 2006

© 2006 Yang et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background
Methylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC).

Methods
The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39) rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p.) on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10). Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min.

Results
Results showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% ± 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% ± 5.9% after 2.5 mg/kg MPD, and 56.5% ± 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of MPD-induced attenuation were also found among these brain areas.

Conclusion
These results suggest that an acute treatment of MPD produces electrophysiologically detectable alterations at the neuronal level, as well as observable, behavioral responses. The present study is the first to investigate the acute dose-response effects of MPD on behavior in terms of locomotor activity and in the brain involving the sensory inputs of VTA, NAc, and PFC neurons in intact, non-anesthetized, freely behaving rats previously implanted with permanent electrodes.
2010-08-08 21:51
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我想你是研究已知药物在大脑的作用,最理想的方式是知道目前临床通常用药量,使用此剂量最简单, 将此剂量从人转化成为动物用量即可。在这样的条件下,仍然需要摸索剂量和生物学效应(体内外)之间的关系,建立所谓的量效关系,如果这方面的数据很少,不然你的结果可靠性很低,不能发表到好刊物上。

如果没有此数据,或此前没有此药对CNS影响的数据,可以根据现有的剂量给药于动物,然后收集动物的cerebral spinal fluid,大脑组织和血液,测定其浓度。

有了这些数据,结合peilei1981说的方法和量效关系,也就是动物的行为学观察,基本可以确定要用的剂量。
2010-08-09 19:37
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我也遇到了和老师一样的问题,只有细胞培养时最佳浓度,没有侧脑室注射浓度和剂量,不知道老师当时是怎么处理这个问题的
2016-08-19 13:13
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