Feller D J, Young E R, Riggan J P, Stuart J, Crabbe J C
Research Service, VA Medical Center, Portland, OR.
Psychopharmacology (Berl). 1993;112(2-3):331-8. doi: 10.1007/BF02244929.
Mice have been selectively bred for genetic sensitivity (COLD) or insensitivity (HOT) to acute ethanol-induced hypothermia. COLD mice readily develop tolerance to the hypothermic effects of ethanol (EtOH) when it is chronically administered, while HOT mice do not. A number of studies have implicated serotonergic systems in both sensitivity and the development of tolerance to the hypothermic and ataxic effects of EtOH. In the experiments reported here, we administered the serotonin (5HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) to HOT and COLD mice before the acute and chronic administration of equipotent doses of EtOH. 5,7-DHT lesions significantly reduced (by about 65%) whole brain levels of 5HT in both selected lines. This treatment reduced sensitivity to acute EtOH hypothermia in COLD, but not in HOT mice, and blocked the development of tolerance only in COLD mice. Metabolites of 5HT, norepinephrine, and dopamine were generally increased in hypothalamic and brain stem tissue after acute EtOH injection, but HOT and COLD mice were not differentially susceptible to these effects. These results suggest that genes affecting 5HT systems may mediate some of the differences in response to the hypothermic effects of EtOH characterizing HOT and COLD mice.
小鼠已被选择性培育出对急性乙醇诱导的体温过低具有遗传敏感性（COLD）或不敏感性（HOT）。当长期给予乙醇（EtOH）时，COLD小鼠很容易对其体温过低效应产生耐受性，而HOT小鼠则不会。许多研究表明，血清素能系统在对EtOH体温过低和共济失调效应的敏感性及耐受性发展中均起作用。在本文报道的实验中，我们在急性和慢性给予等效剂量的EtOH之前，给HOT和COLD小鼠注射血清素（5HT）神经毒素5,7 - 二羟基色胺（5,7 - DHT）。5,7 - DHT损伤显著降低了（约65%）两个选定品系小鼠全脑的5HT水平。这种处理降低了COLD小鼠对急性EtOH体温过低的敏感性，但对HOT小鼠没有影响，并且仅在COLD小鼠中阻断了耐受性的发展。急性注射EtOH后，下丘脑和脑干组织中5HT、去甲肾上腺素和多巴胺的代谢产物通常会增加，但HOT和COLD小鼠对这些影响的易感性没有差异。这些结果表明，影响5HT系统的基因可能介导了HOT和COLD小鼠在对EtOH体温过低效应反应上的一些差异。
