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Attenuation of morphine withdrawal syndrome by macromolecular synthesis inhibitors in rats

Attenuation of the morphine withdrawal syndrome by the combination treatment of morphine and protein/nucleic acid synthesis inhibitors was investigated in rats. Groups of rats were treated twice daily with gradually increasing doses of morphine (4–28 mg/kg) in combination with a protein/nucleic acid synthesis inhibitor (actinomycin D, chloramphenicol, cycloheximide, cytarabine, or tetracycline) for 14 days. Withdrawal was precipitated by naloxone on day 15 and the withdrawal manifestations were scored on a weighted basis for mild, moderate, and severe signs. The mild withdrawal signs were significantly decreased by cytarabine and tetracyline whereas the other combination‐treated groups were only slightly decreased. The moderate and serve withdrawal signs for all combination‐treated groups were significantly suppressed compared to the morphine‐treated group. Therefore, attenuation of the morphine withdrawal syndrome by these protein/nucleic acid synthesis inhibitors supports an involvement of macromolecules in the development of physical dependence.