破壞中樞五羥色胺神經系統增強大白鼠飲酒行為

Central Serotonergic Lesioning Augments Alcohol Drinking in Rats

林子超(Tzu-Chao Lin) ； 廖志飛(Jyh-Fei Liao) ； 王家儀(Jia-Yi Wang)

《Journal of Medical Sciences》 16卷6期 (1996/06) Pp. 373-388

摘要

以往探討腦中五羥色胺神經系統和飲酒行為之研究中，大部分使用幾種近親繁殖所選殖的Wistar品系嗜酒性大白鼠，利用它們飲酒量之差異來探討飲酒行為的生理機制。然而，這些研究都是以未曾飲酒的嗜酒性大白鼠為對象，我們的實驗擬比較酒精偏好度較低的Sprague-Dawley（簡稱SD）品系大白鼠，破壞其中樞五羥色胺神經系統後對飲酒行為之影響，並比較此作用於未曾飲酒（alcohol naive）或長期飲酒之大白鼠是否有差異。實驗結果顯示，小腦延髓池注射5, 7-dihydroxytryptamine（簡稱5, 7-DHT）神經毒素的5-7-DHT組大白鼠比溶媒對照組，有較高的飲酒量，而且兩組之飲水量並無統計差異。中樞給予5, 7-DHT 的5,7-DHT組大白鼠，在大多數的腦區，會顯著降低5-HT及5-HIAA之含量，但對5-HT1A接受器卻不影響其Bmax和KD。另外，由溶媒對照組發現，長期飲酒會使前額皮質區及小腦內5-HT含量及下視丘5-HIAA含量降低。長期飲酒之行為與前額皮質和小腦內5-HT含量降低以及前額皮質和下視丘腦區5-HIAA含量降低有著密切的關聯性。綜合我們的實驗結果，中樞給予5,7-DHT神經毒素後，會明顯地使大部份腦區中5-HT及5-HIAA含量降低，並顯著增加飲酒量及酒精偏好程度。以往在Wistar品系嗜酒性大自鼠發現其腦中五經色胺系統活性降低的現象，如今本實驗用Sprague-Dawley品系大白鼠亦由另一角度證明腦中五體色胺系統活性確實影響飲酒量與酒精之偏好程度。

關鍵字

五羥色胺神經系統 ； 飲酒行為 ； 大白鼠

並列摘要

Ample evidence has accumulated indicating that central serotonin (5-HT) systems are intimately associated with alcohol drinking behavior. The evidence has been largely derived from animal studies, in which alcohol-preferring inbred rats of Wistar origin were used. Previous studies have found lower levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in several brain regions of these rats. However, these studies used alcohol naive animals. The effect of alcohol drinking on central serotonin systems has been seldom studied in these rats. The present study was therefore initiated to compare the effect of central serotonergic lesioning on alcohol consumption in male Sprague-Dawley rats. Central serotonergic neurons were lesioned through the intracisternal injection of the serotonin (5-HT) depleting neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) with pretreament of desipramine (DMI). Control rats were ”sham-lesioned” with the vehicle.Our results indicated that rats in 5, 7-DHT group had significantly higher (p＜0.001) alcohol consumption compared to the sham-lesioned (vehicle treated) group. Water consumption was not different between 5,7-DHT and vehic1e groups. Analyses of tissue levels by HPLCECD indicated that the 5,7-DHT group had significantly lower levels of 5-HT and 5-HIAA in most brain regions in ”alcohol naive” groups and in ”alcohol drinking” groups. Radioligand binding data indicated neither the KD nor the Bmax of serotonin 5-HT1A receptors was significantly different between 5, 7-DHT and vehicle groups of alcohol naive rats and rats with chronic alcohol drinking. These results suggested that central administration of 5, 7- DHT was effective in reducing 5-HT and 5-HIAA levels in most brain regions; however, serotonin 5-HT1A receptors were not affected. Chronic alcohol drinking was associated with lower levels of 5-HT and 5-HIAA in the frontal cortex, 5-HIAA in the hypothalamus and 5-HT in the cerebellum.In conclusion, central administration of 5, 7-DHT significantly lowered concentrations of 5-HT/5-HIAA in most brain regions and significantly augmented alcohol intake and alcohol preference in Sprague Dawley rats.

並列關鍵字

central serotonin systems ； alcohol drinking behavior ； rats