Sex-specific transgenerational effects of morphine exposure on reward and affective behaviors.

Current estimates indicate that millions of people in the United States abuse opioid drugs, which may also affect their offspring. To determine whether parental exposure to morphine alters reward and affective behaviors in subsequent generations we exposed male and female C57BL/6NTac mice to morphine (75 mg) or placebo pellets for 4 weeks. Naïve mice were used as mating partners to create subsequent generations (F1 and F2). Adult male and female F1 and F2 mice were tested in the morphine conditioned place preference paradigm (CPP), marble burying (MB), acoustic startle response (ASR), and open field tests (OFT). Paternal morphine exposure resulted in significantly attenuated preference scores amongst F1 male offspring, but significantly higher preference scores amongst F1 female offspring at the lowest CPP dose tested (5 mg/kg). In contrast, maternal exposure to morphine did not affect morphine reward in the F1 generation; however, the F2 male offspring of morphine-exposed F0 females displayed significantly higher CPP preference scores. Preference scores in F2 females were not affected by F0 male or female morphine exposure. Sex-specific alterations in affective behaviors were observed only in the offspring of F0 males exposed to morphine with F1 males spending less time in the center of the open field and F1 females spending more time in the center of the open field. One generation later, affective behaviors were no longer altered in F2 males but F2 females from the F0 male morphine exposure buried more marbles in the MB test. In summary, early exposure to morphine in males and females causes lineage-specific inheritance of reward and affective behaviors.