SEROTONIN AND GENETIC-DIFFERENCES IN SENSITIVITY AND TOLERANCE TO ETHANOL HYPOTHERMIA

Mice have been selectively bred for genetic sensitivity (COLD) or inse nsitivity (HOT) to acute ethanol-induced hypothermia. COLD mice readil y develop tolerance to the hypothermic effects of ethanol (EtOH) when it is chronically administered, while HOT mice do not. A number of stu dies 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 be fore the acute and chronic administration of equipotent doses of EtOH. 5,7-DHT lesions significantly reduced (by about 65%) whole brain leve ls of 5HT in both selected lines. This treatment reduced sensitivity t o acute EtOH hypothermia in COLD, but not in HOT mice, and blocked the development of tolerance only in COLD mice. Metabolites of 5HT, norep inephrine, and dopamine were generally increased in hypothalamic and b rain stem tissue after acute EtOH injection, but HOT and COLD mice wer e not differentially susceptible to these effects. These results sugge st that genes affecting 5HT systems may mediate some of the difference s in response to the hypothermic effects of EtOH characterizing HOT an d COLD mice.