Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats
Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats
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DOI：
10.3171/2010.4.focus10105
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发表时间：
2010-08-01
影响因子：
4.1
通讯作者：
Leiter, James C.
中科院分区：
文献类型：
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作者：
Henderson, Michael B.;Green, Alan I.;Leiter, James C.
对象。作者验证了一个假设，即在每只嗜酒(P)大鼠建立稳定的大量酒精摄入量后，以及在已建立酒精摄入量的P大鼠被剥夺酒精4-6周后，对伏隔核（NAcc）进行脑深部刺激（DBS）会减少酒精摄入量。双极刺激电极通过立体定向坐标置于NAcc两侧。在第一项研究中，P大鼠（9只动物）在大约2周的时间内建立稳定的酒精摄入模式（约5-7 g/天），研究脑深部电刺激（140-150 Hz， 60 μ s脉宽，200 μ a电流强度）对NAcc酒精摄入和酒精偏好的急性影响。每只动物作为自己的对照，在连续两天的每一天接受1小时的DBS和1小时的假DBS，反之亦然。测试顺序（假DBS vs DBS）是随机的。在第二项研究中，每只动物被允许建立一个稳定的酒精摄入量，然后动物被剥夺酒精4-6周。从每只动物重新引入酒精开始，动物在NAcc中接受DBS（6只大鼠）或假DBS（5只大鼠）24小时。在相同的动物中，与一段时间的假dbs治疗相比，NAcc脑深部电刺激急剧降低了酒精偏好。此外，在强制戒酒后的前24小时内，与假治疗组相比，DBS组的酒精消费量和偏好显著减少。NAcc在药物滥用的奖励和随后的成瘾特性中起着关键作用，特别是酒精。脑深部电刺激在急性和酒精剥夺一段时间后减少了P大鼠的酒精消耗。因此，脑深部电刺激与其他神经生理测量相结合，可能是确定NAcc在中皮质边缘奖赏回路中的作用的有用工具。在NAcc中进行深部脑刺激也可能是一种有效的治疗方法，用于减少滥用酒精并且对其他形式的治疗没有反应的患者的酒精摄入量。(DOI: 10.3171 / 2010.4.focus10105)
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-mu sec pulse width, and 200-mu A 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. (DOI: 10.3171/2010.4.FOCUS10105)