LETHAL AND SUBLETHAL EFFECTS ON THE PROGENY OF MALE RATS TREATED WITH METHADONE

Abstract

Fourteen male rats were treated with methadone HCl (METH) 10 mg/kg s.c. per day (or 12 days. Fifteen control males received saline injections for four days. Each male was caged with four drug-naive females each night. METH males lost weight over the treatment period and mated less frequently. At autopsy, their seminal vesicle weight was decreased, even when corrected for body weight. Progeny of METH males (507 pups) were of lower average birth weight than controls (276). Prior copulation had a differential effect, resulting in slightly heavier control pups but significantly decreased birth weights in the METH group. Neonatal mortality of the METH progeny was 18.2%, compared to 9.5% of the controls (P < .01). Mortality was related in a complex fashion to number of drug exposures and previous sexual experience of the sire. Male offspring were particularly affected. Ponderal growth of survivors from litters with high neonatal death rates was diminished, with females being significantly lighter at 75 and 132 days of age. Open field defecation scores were significantly different at two but not at four months of age. No differences in acquisition of a conditioned avoidance response were noted. These results together with previous data from our laboratory establish for the first time lethal and sublethal effects on the progeny of a drug-treated sire.

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