Disposition of ethanol and its effect on rectal temperature in morphine-dependent, morphine-abstinent and...

Rats were treated chronically with twice daily injections of morphine hydrochloride in gradually increasing doses from 20 to 200 mg/kg for 22 consecutive days. Rats in a control group were injected with 0.9% NaCl. At 1 hour after the last injection of morphine (dependent state) and at 3 and 16 days after abrupt withdrawal (abstinent state) the animals were injected intraperitoneally with 2.0 g/kg ethanol. Blood ethanol concentrations (tail blood) and rectal temperatures were determined at 30-60 min. intervals for up to 7 hours. The absorption of ethanol was slower in rats treated with morphine and the time taken to reach the end of the blood concentration curve was increased. This implies a slower turnover of ethanol in morphine-dependent and abstinent rats. At 16 days after withdrawal, the blood ethanol profiles were the same as in control rats not exposed to morphine. Injection of morphine (200 mg/kg) intolerant animals caused a pronounced hyperthermia which lasted for about 4 hours. Ethanol treatment rapidly counteracted the rise in body temperature. Morphine abstinent rats showed a hypothermic response to ethanol. The altered disposition of ethanol in acute withdrawal may result from physiological disturbances such as impaired fluid balance, dehydration, altered peripheral blood flow and poor nutritional status. There was no evidence for a faster rate of ethanol metabolism in the hypermetabolic state associated with morphine tolerance and dependence.