Maternal exposure to buprenorphine, but not methadone, during pregnancy reduces social play behavior across two generations of offspring.

Rationale: The prevalence of newborns exposed to medications for opioid use disorder (MOUD), such as methadone or buprenorphine, during pregnancy is increasing. The opioid system plays a crucial role in regulating and shaping social behavior, and children prenatally exposed to opioids face an increased risk of developing behavioral problems. However, the impact of prenatal exposure to MOUD on offspring's social behavior during adolescence and adulthood, as well as potential intergenerational effects, remains largely unexplored.

Objectives: Our study employed a translationally relevant animal model to investigate how maternal (F0) exposure to MOUD during pregnancy affects social behavior in young and adult rats across the first (F1) and second (F2) generation of offspring.

Methods: Female Sprague-Dawley rats were implanted with an osmotic minipump delivering methadone (10 mg/kg/day), buprenorphine (1 mg/kg/day), or sterile water, prior to mating with drug-naïve males. Adult F1 females were mated with treatment-matched F1 males to generate F2 offspring. We assessed social play behavior in juvenile offspring, and social interaction behavior in a three-chamber social interaction test in young adults of the F1 and F2 generations.

Results: Maternal exposure to buprenorphine, but not methadone, during pregnancy reduced social play behavior in both F1 and F2 offspring, expressed by a reduced number of pounces and pins, which are the two most characteristic parameters of social play in rats. Adult social interactions were unaffected by prenatal MOUD exposure across both generations.

Conclusions: Maternal exposure to buprenorphine during pregnancy may have adverse effects on social play behavior across two generations of offspring.