Inhibitory by d,1-methadone of RNA and protein synthesis in neonatal mice: Antagonism by naloxone or naltrexone

Neonatal mice were injected once daily with d,1-methadone in a dosage of 2 mg/kg. The remaining half of the litter was injected with saline. After one week the incorporation of labeled uridine and labeled leucine was significantly (P < 0.05) reduced in skeletal muscle. Longer treatment with methadone impaired RNA and protein synthesis in liver, heart, skeletal muscle and brain. The percentage reduction in RNA was log-dose related. When methadone was discontinued for 1 week following 4 weeks of treatment, incorporation of precursors into RNA and protein was found to be normal. A specific opioid effect is suggested by the finding that naltrexone or in part, nalaxone, given concomitantly with the methadone prevents development of the biochemical lesion.