Melchior C L, Tabakoff B
Pharmacol Biochem Behav. 1986 Apr;24(4):955-61. doi: 10.1016/0091-3057(86)90442-9.
In order to assess the role of the serotonergic system in the development of tolerance to ethanol in the mouse, serotonin neurons in the CNS were lesioned with an intracerebroventricular injection of the neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Mice injected with 5,7-DHT responded to an acute dose of ethanol with a longer sleep time and greater fall in body temperature than CSF-treated mice. The increased response to acute administration of ethanol was accompanied by higher circulating levels of ethanol in mice pretreated with 5,7-DHT. When mice were fed an ethanol-containing liquid diet for five days, a higher mortality rate was observed in the 5,7-DHT group compared to the CSF pretreated group of mice. When the groups of mice were tested for tolerance 24 hours after withdrawal, the 5,7-DHT group was less tolerant than the CSF group. Therefore, damage to the serotonin neurons results in altered ethanol disposition, altered initial sensitivity to ethanol, and an inhibition in the development of tolerance in the mouse.
为了评估血清素能系统在小鼠对乙醇耐受性发展中的作用，通过脑室内注射神经毒素5,7 - 二羟基色胺（5,7 - DHT）损毁中枢神经系统中的血清素神经元。与注射脑脊液的小鼠相比，注射5,7 - DHT的小鼠对急性剂量乙醇的反应是睡眠时间更长，体温下降幅度更大。对急性给予乙醇反应的增强伴随着5,7 - DHT预处理小鼠体内乙醇循环水平的升高。当给小鼠喂食含乙醇的液体饮食五天时，与脑脊液预处理的小鼠组相比，5,7 - DHT组观察到更高的死亡率。当在撤药24小时后对小鼠组进行耐受性测试时，5,7 - DHT组的耐受性低于脑脊液组。因此，血清素神经元的损伤导致小鼠体内乙醇处置改变、对乙醇的初始敏感性改变以及耐受性发展受到抑制。
