戒断相关内感受对大鼠吗啡觅药行为的诱导及其岛叶的调控机制

PSYCH OpenIR > 健康与遗传心理学研究室

	戒断相关内感受对大鼠吗啡觅药行为的诱导及其岛叶的调控机制
其他题名	The role of Insular Cortex in Facilitation of Morphine-Seeking Behavior by Peripheral Withdrawal in Rats
	李春禄
	2013-05
摘要	维持内稳态是生存的前提。因此，内感受（机体对内部状态的感觉），特别是负性的内感受，与情绪和动机密切相关。近几年，内感受皮层-岛叶在尼古丁成瘾中的作用受到越来越多的关注。然而内感受在阿片觅药动机中的作用仍不清楚。内感受参与成瘾的机制可能与药物的奖赏相关的正强化和戒断相关的负强化有关，而这两种强化过程是阿片成瘾形成和维持的重要因素。岛叶包括后部的初级内感受皮层（GI）和前部的高级（higher-order）内感受皮层（AI）。其中GI主要接收感觉信息，而AI与边缘系统联系密切。因此，这两个亚区可能在内感受参与成瘾的过程中具有不同的功能，AI可能更重要。岛叶向动机相关脑区发出大量纤维投射，而β-肾上腺素受体可以调控岛叶内投射神经元的活动。提示岛叶内的β-肾上腺素受体可能是内感受调控觅药动机的重要基础之一。为了验证以上假设，我们使用条件性位置偏爱（CPP）和条件性位置厌恶（CPA）的获得来衡量药物相关的正性和戒断相关的负性强化特性；通过外周戒断（腹腔注射M纳洛酮，不能通过血脑屏障）对CPP表达的影响，量化戒断相关的内感受对觅药行为的调控；并结合脑内局部微量给药技术，考察和比较AI和GI及其内的β-肾上腺素受体的作用。结果发现： 1）、失活GI而非AI损害了吗啡诱发的CPP的获得；失活AI或GI均可以损害戒断诱发的CPA的获得。 2）、外周戒断和腹腔注射氯化锂均可以增强CPP的表达；并且两种处理均可以诱发CPA。 3）、失活AI和GI均可以损害外周戒断诱发的CPP表达的增强和外周戒断诱发的CPA的获得。 4）、阻断AI和GI内的β-肾上腺素受体可以损害外周戒断诱发CPA的获得；然而只有阻断AI的β-肾上腺素受体可以损害外周戒断诱发CPP表达的增强。以上结果表明，内感受参与吗啡成瘾相关的正性和负性强化过程；戒断相关的内感受具有厌恶的动机性，且可以增强觅药行为；AI和GI均参与戒断相关内感受的厌恶动机及其对觅药行为的调控；AI和GI内的β-肾上腺素受体均参与戒断相关内感受的厌恶动机，但AI而非GI内的β-肾上腺素受体参与戒断相关的内感受对觅药行为的调控。提示AI在戒断相关的负性内感受对觅药行为的调控中发挥更重要的作用。
其他摘要	The bodily changes underlie the reinforcing properties of drugs/withdrawal, at least at initial stages of addiction. Therefore, interoceptive system, particularly insular cortex, might play an important role in positive and negative reinforcement related with drug addiction. However, the insula is divided into two major subdivisions, the primary interoceptive posterior granular insula (GI) and the high-order anterior agranular insula (AI). Their neural connections suggest their functional heterogeneity. Further, evidences reveal that the β-adrenergic agonists/ antagonists could modulate the activity of insular pyramidal cells, which innervate the brain areas related to drug-seeking behavior. These evidences suggest that β-adrenergic receptor is involved in the modulation of interoception on drug-seeking behavior. To address these issues, we chose morphine-induced CPP and conditioned place aversion (CPA) induced by naloxone-precipitated acute morphine withdrawal as behavioral paradigms of positive and negative affective learning, respectively; to determine the effect of interoception related with withdrawal on drug seeking behavior more definitely, we examine the effect of peripheral withdrawal on the expression of morphine-induced CPP ; we inactivated the AI/GI or blockade β-adrenergic receptors before the training of conditioned place aversion (CPA)/ expression of CPP, to examine the role of AI/GI and the β-adrenergic receptors in these two areas on the modulation of peripheral withdrawal on drug-seeking behavior We found that 1) inactivation of GI but not that of AI attenuated the acquisition of morphine-induced CPP; both AI and GI inactivation attenuated the acquisition of naloxone-precipitated CPA; 2) both peripheral withdrawal and Lithium chloride (i.p.) could facilitate the expression of CPP and induce a CPA; 3) both AI and GI inactivation impaired the facilitation of the expression of CPP and the acquisition of CPA induced by peripheral withdrawal; 4) blockage of β-adrenergic receptors in AI/GI disrupted the acquisition of CPA induced by peripheral withdrawal; however, blockage of β-adrenergic receptors in AI but not GI impaired the facilitation of the expression of CPP induced by peripheral withdrawal. These results suggested that interoception is involved in the positive and negative reinforcement related with morphine addiction; peripheral withdrawal had aversive motivation, and can effectively drive the drug seeking behavior; both AI and GI are critical for those two processes; β-adrenergic receptors in both AI and GI underlie the aversive motivation of peripheral withdrawal; however, β-adrenergic receptors in AI but not GI appear crucial for the facilitation of morphine-seeking behavior induced by peripheral withdrawal, suggesting AI is more important than GI on the effect of interoception related with opiate withdrawal on the drug-seeking behavior.
学科领域	医学心理学
关键词	戒断内感受觅药行为岛叶 AI GI β-肾上腺素受体
学位类型	博士
语种	中文
学位专业	心理学
学位授予单位	中国科学院研究生院
学位授予地点	北京
文献类型	学位论文
条目标识符	http://ir.psych.ac.cn/handle/311026/19612
专题	健康与遗传心理学研究室
作者单位	中国科学院心理研究所
推荐引用方式 GB/T 7714	李春禄. 戒断相关内感受对大鼠吗啡觅药行为的诱导及其岛叶的调控机制[D]. 北京. 中国科学院研究生院,2013.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
李春禄-博士学位论文.pdf（1574KB）	学位论文		限制开放	CC BY-NC-SA	请求全文