Chronic methadone administration to male rats: tolerance to adverse effects on sires and their progeny

Previous studies have shown that acute administration of methadone to male rats prior to mating results in adverse effects on their progeny, particularly decreased birth weights and increased neonatal mortality. Rather than chronic administration accentuating these effects, results of the present study indicate that tolerance developed so that no adverse effects were found in offspring sired after 21--32 days of methadone administration. In the sire, maintenance of normal weights of accessory sex glands after 4 months of daily methadone suggests that tolerance developed to the CNS effect(s) responsible for the depressed serum LH and testosterone levels found after acute administration of narcotics. In contrast, tolerance did not develop to the inhibition of weight gain produced by methadone administration. No evidence for a dominant lethal effect could be found after chronic methadone administration, in contrast to suggestive evidence for this effect found in previous experiments after acute methadone administration.