Cross-Tolerance between Ethanol and Morphine

Abstract

Adult male Wistar rats were fed chronically a liquid diet providing 35% of the calories as ethanol (10–12 g/kg ethanol daily), while pair-fed controls received the corresponding diet with alcohol replaced by an equicaloric concentration of sucrose. Rectal tempera tures, after test doses of ethanol or morphine, were measured in several groups of rats at various times during chronic ethanol treatment. The fall in rectal temperature after a challenge dose of ethanol (3.0 g/kg) was significantly lower in the chronic alcohol group than in controls, indicating tolerance to ethanol-induced hypothermia. The same animals also developed cross-tolerance to the hypothermic effect of morphine (15 and 30 mg/kg), but not to the hyperthermic effect of morphine (5 mg/kg). Administration of morphine (30 mg/kg i.p.) for 3 days resulted in tolerance to morphine hypothermia, and cross-tolerance to ethanol-induced hypothermia. These studies fit with our hypothesis that tolerance and cross-tolerance among drugs develop to drug effects rather than to drug per se. Therefore drugs sharing a common effect, even by different mechanisms, might show cross-tolerance for that effect.