Morphine依存ラットに対するMetyraponeの効果

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Gibson and Pollock recently reported that metyrapone, a relatively specific 11-B-hydroxylase inhibitor, abolished the pronounced fall in body weight which was observed during morphine withdrawal. The present study was carried out in an attempt to confirm their observation and, in addition, to assess whether or not such an effect might be related to the adrenal effect of metyrapone. In male SD strain rats treated with morphine-admixed food for 7 days, abstinence syndrome such as dramatic decreases in body weight and food intake as well as diarrhea appeared when morphine-admixed food was substituted by a regular diet. The abstinence syndrome by morphine withdrawal in animals treated with a combination of morphine and metyrapone for 7 days was significantly mild. Metyrapone also inhibited the abstinence syndrome which occurred when levallorphan was given. However, metyrapone itself did not affect the body weight and the food intake of normal rats. In morphine dependent rats which were subjected to adrenalectomy prior to morphine treatment, a similar abstinence syndrome following morphine withdrawal appeared, and an inhibition of the syndrome by a combination of morphine and metyrapone was also observed, as was seen in animals with the intact adrenals. On the other hand, we found using the hot plate method that metyrapone did not suppress the morphine analgesia in normal rats, but rather enhanced it. These results indicate that metyrapone inhibits morphine abstinence syndrome specifically, without inhibiting the analgesic effect of morphine and also that the inhibition of the abstinence syndrome by metyrapone is due to an effect other than that of metyrapone on the adrenal function.
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Morphine依存ラットに対するMetyraponeの効果

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