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伏隔核深部脑刺激可减少酒精偏好大鼠的酒精摄入量。

Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats.

机构信息

Department of Neurosurgery, Dartmouth Medical School, Lebanon, New Hampshire, USA.

出版信息

Neurosurg Focus. 2010 Aug;29(2):E12. doi: 10.3171/2010.4.FOCUS10105.

Abstract

OBJECT

The authors tested the hypothesis that deep brain stimulation (DBS) in the nucleus accumbens (NAcc) decreases alcohol intake in alcohol-preferring (P) rats after each animal has established a stable, large alcohol intake and after P rats with an established intake have been deprived of alcohol for 4-6 weeks.

METHODS

Bipolar stimulating electrodes were bilaterally placed in the NAcc using stereotactic coordinates. In the first study, P rats (9 animals) were allowed to establish a stable pattern of alcohol intake (about 5-7 g/day) over approximately 2 weeks, and the acute effects of DBS in the NAcc (140-150 Hz, 60-microsec pulse width, and 200-microA current intensity) on alcohol intake and alcohol preference were studied. Each animal acted as its own control and received 1 hour of DBS followed by 1 hour of sham-DBS or vice versa on each of 2 sequential days. The order of testing (sham-DBS vs DBS) was randomized. In the second study, each animal was allowed to establish a stable alcohol intake and then the animal was deprived of alcohol for 4-6 weeks. Animals received DBS (6 rats) or sham-DBS (5 rats) in the NAcc for 24 hours starting when alcohol was reintroduced to each animal.

RESULTS

Deep brain stimulation in the NAcc, as compared with a period of sham-DBS treatment in the same animals, acutely decreased alcohol preference. Furthermore, alcohol consumption and preference were significantly reduced in the DBS group compared with the sham treatment group during the first 24 hours that alcohol was made available after a period of forced abstinence.

CONCLUSIONS

The NAcc plays a key role in the rewarding and subsequent addictive properties of drugs of abuse in general and of alcohol in particular. Deep brain stimulation in the NAcc reduced alcohol consumption in P rats both acutely and after a period of alcohol deprivation. Therefore, DBS in the NAcc coupled with other neurophysiological measurements may be a useful tool in determining the role of the NAcc in the mesocorticolimbic reward circuit. Deep brain stimulation in the NAcc may also be an effective treatment for reducing alcohol consumption in patients who abuse alcohol and have not responded to other forms of therapy.

摘要

目的

作者通过测试假设,即刺激伏隔核(NAcc)中的深部脑刺激(DBS)是否可以在每只动物建立稳定且大量的酒精摄入量后,以及在建立摄入量的酒精偏好(P)大鼠被剥夺酒精 4-6 周后,减少 P 大鼠的酒精摄入量。

方法

使用立体定向坐标,将双极刺激电极双侧放置在 NAcc 中。在第一项研究中,允许 P 大鼠(9 只动物)在大约 2 周内建立稳定的酒精摄入量模式(约 5-7 g/天),并研究 NAcc 中的 DBS(140-150 Hz、60-微秒脉冲宽度和 200-微安电流强度)对酒精摄入量和酒精偏好的急性影响。每个动物作为自己的对照,在连续两天中的每两天中接受 1 小时的 DBS 治疗,然后接受 1 小时的假 DBS 治疗,或者反之亦然。测试顺序(假 DBS 与 DBS)是随机的。在第二项研究中,允许每个动物建立稳定的酒精摄入量,然后将动物剥夺酒精 4-6 周。当每个动物重新摄入酒精时,动物在 NAcc 中接受 24 小时的 DBS(6 只动物)或假 DBS(5 只动物)治疗。

结果

与同一动物的假 DBS 治疗期相比,NAcc 中的深部脑刺激可急性降低酒精偏好。此外,与假处理组相比,在强制禁欲期结束后首次提供酒精的前 24 小时内,DBS 组的酒精消耗和偏好显著降低。

结论

NAcc 在一般药物滥用和特别是酒精的奖赏和随后的成瘾特性中起着关键作用。NAcc 中的深部脑刺激既可以急性减少 P 大鼠的酒精摄入量,也可以减少酒精剥夺后的酒精摄入量。因此,NAcc 中的 DBS 结合其他神经生理测量可能是确定 NAcc 在中脑边缘奖赏回路中的作用的有用工具。NAcc 中的深部脑刺激也可能是减少对其他治疗形式无反应的滥用酒精的患者的酒精消耗的有效治疗方法。

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