Chlorpromazine and Dithioerythritol Protection against Acute Ethanol Toxicity

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Abstract
Our previous work has shown that an increase in body temperature increases the acute toxicity of ethanol in mice. To determine whether a decrease in body temperature would have the opposite effect, we studied the effect of two substances that decrease body temperature (chlorpromazine (CPZ) and dithioerythrrtol (DTE)) on ethanol toxicity. Matched groups of 10 mice were injected sc with CPZ (5 mg/kg), DTE (80 mg/kg), or saline (controls). CPZ and DTE significantly depressed the rectal temperature to 32.8 and 34.5°C, respectively. One hour later, all three groups received a specified dose of ethanol (6.5-10.7 g/kg, 24% w/v, intraperitoneal). The experiment was repeated 17 times at different ethanol doses. The pretreatments increased the 1 hr LDM from 7.8 ±0.1 g/kg for the controls to 8.6 ± 0.2 g/kg (DTE) and 10.0 ± 0.3 g/kg (CPZ) (p < 0.001). The protective effect of CPZ was maximal around 5 mg/kg, and less at both lower and higher CPZ doses. When the temperature drop was prevented by directly heating the mice, the protective effect of DTE could be eliminated, but the effect of CPZ was only partially prevented. Placing the CPZ-treated mice in a warmer environment only produced a major reversal of CPZ protection when rectal temperature reached 38°C. In conclusion, CPZ and DTE both decrease body temperature and protect against acute ethanol toxicity. The protection seems to be due at least partially to the decrease in body temperature prior to ethanol injection.