Morphine Withdrawal in the Rat: Assessment by Quantitation of Diarrhea and Modification by Ethanol

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Abstract
A procedure to quantitatively assess diarrhea during morphine withdrawal in rats has been developed. Physical dependence on morphine was produced either by pellet implantation (75 mg morphine/rat) or by a single subcutaneous injection of morphine (150 mg/kg in oil). The gross morphine abstinence signs observed after naloxone administration included diarrhea, body weight loss, jumping, wet-dog shakes, hypothermia, teeth chattering, and irritability to handling. A dose-response relationship was observed for naloxone-precipitated withdrawal diarrhea, with an optimal naloxone dose of 0.4 mg/kg. The severity of diarrhea was dependent on the interval after morphine withdrawal prior to naloxone administration. The probably direct relationship between diarrhea (measured as total excrement) and body weight loss during narcotic withdrawal was documented. Morphine withdrawal diarrhea was found to be a useful index for the study of the effects of other drugs on morphine withdrawal. Ethanol (0.5–2.0 g/kg) was found to suppress diarrhea, wet-dog shakes and jumping, but enhance hypothermia during morphine withdrawal; these effects of ethanol were dose-dependent. The suppression of morphine withdrawal diarrhea by ethanol (2 g/kg) was prolonged, lasting up to 20 h. This suppression of withdrawal diarrhea by ethanol is nonspecific since ethanol also suppressed diarrhea induced by castor oil feeding and also gastrointestinal motility as measured by the movement of charcoal in the intestine after charcoal meal feeding. Suppression of some aspects of the morphine withdrawal syndrome by ethanol may account in part for the increase in ethanol consumption in that setting in rats and possibly also in man.

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