Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal
Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal
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DOI：
10.1016/0306-4522(90)90106-e
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发表时间：
1990-12
期刊：
影响因子：
3.3
通讯作者：
L. Stinus;M. Moal;G. Koob
中科院分区：
文献类型：
--
作者：
L. Stinus;M. Moal;G. Koob
阿片类药物戒断综合征的具体大脑部位一直难以描绘，而典型的明显戒断症状，如湿狗抖动，眼睑下垂和牙齿抖动，似乎在大脑中广泛存在。使用一个更一般的动机测试，涉及依赖大鼠的操作性行为的中断，大脑的网站最敏感的反应破坏性的影响，脑内给药的阿片拮抗剂，甲基纳洛溴铵，是该地区的延髓核，一个网站也牵连在阿片类药物的急性增强性能。这种操作性反应的中断被假设为反映了阿片类药物戒断的厌恶性质。本研究直接测试了这一假设，探讨是否intercerebral管理的甲基纳洛铵产生厌恶刺激的影响，测量的位置厌恶的形成。大鼠脑室内植入或双侧插管，旨在内侧背侧丘脑，导水管周围灰质，腹侧被盖区，杏仁核或延髓核皮下植入两个75毫克吗啡丸依赖于吗啡。然后，通过将不同的环境（具有不同纹理、标记和气味的三臂盒子的三个臂之一）与脑室内或脑内单次注射甲基纳洛铵配对，对动物进行位置厌恶训练。结果表明，在高剂量的甲基纳洛铵（1000-2000 ng），所有的网站产生了一个位置厌恶。然而，较低剂量（250-500纳克）产生了显着的大脑部位的选择性与区域的丘脑核最敏感。在注射高剂量甲基纳洛溴铵后进行的观察性测量显示，在将甲基纳洛溴铵注射到中脑腹外侧核和导水管周围灰质后，特别观察到激越。在任何剂量或部位均未观察到腹泻。虽然注射甲基纳洛铵到杏仁核产生的地方厌恶，有没有其他的戒断症状observed.Results结果表明，该地区的延髓核和杏仁核是至关重要的阿片类药物戒断的厌恶刺激效应。
Specific brain sites for the opiate abstinence syndrome have been elusive to delineate, and the classic overt signs of withdrawal such as wet dog shakes, ptosis and teeth chattering appear to be widely represented in the brain. Using a more general motivational test involving a disruption of operant behavior in dependent rats, the brain site most sensitive to the response disruptive effects of intracerebral administration of the opiate antagonist, methylnaloxonium, was the region of the nucleus accumbens, a site also implicated in the acute reinforcing properties of opiates. This disruption of operant responding was hypothesized to reflect the aversive properties of opiate withdrawal. The present study directly tested that hypothesis by exploring whether intercerebral administration of methylnaloxonium produced aversive stimulus effects as measured by the formation of place aversions. Rats implanted intracerebroventricularly or with bilateral cannulae aimed at the medial dorsal thalamus, periaqueductal gray, ventral tegmental area, amygdala or nucleus accumbens were made dependent on morphine by subcutaneous implantation of two 75-mg morphine pellets. The animals were then subjected to place aversion training by pairing of a distinct environment (one of three arms of a three-armed box with distinct texture, markings and smell) with a single injection of methylnaloxonium intracerebroventricularly or intracerebrally. Results showed that at high doses of methylnaloxonium (1000–2000 ng) all sites produced a place aversion. However, lower doses (250–500 ng) produced a significant brain site selectivity with the region of the nucleus accumbens the most sensitive. Observational measurements taken during the postinjection period with the high dose of methylnaloxonium showed that agitation was particularly observed following methylnaloxonium administration into the nucleus accumbens and periaqueductal gray. No diarrhea was observed with any dose or site. Although injections of methylnaloxonium into the amygdala produced place aversion, there were no other abstinence signs observed.Results suggest that the region of the nucleus accumbens and the amygdala are critically involved in the aversive stimulus effects of opiate withdrawal.