外侧缰核在酒精成瘾所致认识和睡眠障碍中的作用和可能机制

发布时间：2019-05-17 23:18

【摘要】：易成瘾的特性使酒精成为最常见的滥用物质之一。鉴于缰核的纤维联系特点,我们决定研究外侧缰核在慢性酒精摄取中对认知和睡眠的调节作用和酒精成瘾所致神经适应的可能机制。为了评价外侧缰核在慢性酒精摄取后的作用,我们采用间歇性给予20%酒精两瓶选择饮用模式。为了研究外侧缰核在抑郁中的作用,我们选用了两种行为学实验：强迫游泳实验和旷场实验。为了研究外侧缰核对认知的作用,我们选择了另外两种行为学实验：Morris水迷宫和新事物识别实验。为了评价酒精摄取的效应和外侧缰核在昼夜节律和睡眠中的作用,我们选择了两个相对独立的试验：跑轮试验和脑电记录。为了确定外侧缰核在酒精成瘾中有作用,我们研究了缰核中的FosB/△FosB表达情况。根据我们的研究,以下试验结果证实缰核在慢性酒精摄取后,对抑郁、认知和睡眠的有重要的调节作用： (1)外侧缰核损毁导致大鼠对酒精的摄取增加,这可能是由于外侧缰核损毁导致其对VTA的抑制作用解除。 (2)缰核损毁的大鼠在强迫游泳中不动时间下降,这可能是中缝背核5-羟色胺水平增加使抑郁大鼠的行为反应增强。 (3)外侧缰核损毁后大鼠空间记忆能力明显减弱,这种效应在摄取酒精的大鼠中更为明显。提示酒精的摄取会加重认知功能障碍。 (4)外侧缰核损毁后显著降低大鼠对新事物的探索时间,表明外侧缰核损毁导致大鼠的物体识别记忆能力减弱。 (5)慢性自我酒精摄取显著增加纹状体和海马的FosB/△FosB阳性细胞数,进一步证实了FosB/△FosB在相关脑区的表达是慢性物质滥用的一种普遍现象。 (6)缰核(内侧缰核和外侧缰核)中FosB/△FosB阳性细胞数增加,证明缰核在酒精成瘾中发挥了作用,进一步表明缰核在成瘾中有重要作用。 (7)外侧缰核损毁改变了大鼠白天的活动量,这可能是外侧缰核的损毁,导致缰核对中缝核的5-羟色胺能神经元的传出纤维遭到破坏,而中缝核在光调节的和非光调节的节律中有重要作用。 (8)我们的观察结果证明,外侧缰核损毁的大鼠夜间睡眠时间减少。有其他研究表明,外侧缰核损毁后大鼠的快动眼睡眠期缩短,睡眠模式也发生改变。这与我们的观察结果是一致的。这也支持了缰核是一个调节昼夜节律和睡眠的核团
[Abstract]:Addictive properties make alcohol one of the most common abusers. In view of the fiber connection characteristics of habenular nucleus, we decided to study the cognitive and sleep regulation of lateral habenular nucleus in chronic alcohol uptake and the possible mechanism of neuroadaptation induced by alcohol addiction. In order to evaluate the effect of lateral habenular nucleus on chronic alcohol intake, we used intermittent 20% alcohol to choose drinking mode. In order to study the role of lateral habenular nucleus in depression, we selected two behavioral experiments: forced swimming test and open field test. In order to study the effect of lateral habenular nucleus on cognition, we chose two other behavioral experiments: Morris water maze and new thing recognition experiment. In order to evaluate the effect of alcohol uptake and the role of lateral habenular nucleus in circadian rhythm and sleep, we chose two relatively independent tests: running wheel test and EEG recording. In order to determine the role of lateral habenular nucleus in alcohol addiction, we studied the expression of FosB/ FosB in habenular nucleus. According to our study, the following results confirmed that habenular nucleus plays an important role in regulating depression, cognition and sleep after chronic alcohol uptake: (1) the damage of lateral habenular nucleus leads to an increase in alcohol uptake in rats. This may be due to the removal of the inhibitory effect of lateral habenular nucleus on VTA. (2) the immobility time of rats with habenular nucleus lesion decreased during forced swimming, which may be due to the increase of serotonin level in dorsal raphe nucleus and the enhancement of behavioral response in depressed rats. (3) after the lesion of lateral habenular nucleus, the spatial memory ability of rats was significantly decreased, especially in rats with alcohol intake. It is suggested that alcohol intake will aggravate cognitive impairment. (4) after lateral habenular nucleus lesion, the exploration time of new things in rats was significantly decreased, which indicated that the damage of lateral habenular nucleus resulted in the decrease of object recognition and memory ability in rats. (5) chronic self-alcohol uptake significantly increased the number of FosB/ FosB positive cells in striatum and hippocampus, which further confirmed that the expression of FosB/ FosB in related brain regions was a common phenomenon of chronic substance abuse. (6) the number of FosB/ FosB positive cells in habenular nucleus (medial habenular nucleus and lateral habenular nucleus) increased, which proved that habenular nucleus played an important role in alcohol addiction, which further indicated that habenular nucleus played an important role in addiction. (7) the lesion of the lateral habenular nucleus changed the activity of the rat during the day, which may be the damage of the lateral habenular nucleus, resulting in the destruction of the efferent fibers of the serotonin neurons in the habenular nucleus to the raphe nucleus. The raphe nucleus plays an important role in photoregulated and non-photoregulated rhythms. (8) our results showed that the nocturnal sleep time of rats with lateral habenular nucleus lesion decreased. Other studies have shown that after lateral habenular nucleus lesion, the fast eye movement sleep period of rats is shortened and the sleep pattern is also changed. This is consistent with our observations. This also supports that the habenular nucleus is a nucleus that adjusts circadian rhythm and sleep.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R749.62

【共引文献】