Substance Abuse Transmission-Impact of Parental Exposure to Nicotine/Alcohol on Regenerated Planaria Offspring

There is an unprecedented global mental health crisis, and substance abuse among youth is a growing issue. According to the Centers for Disease Control and Prevention, 40 million adults in the United States smoke cigarettes, and 4.7 million children have used at least one tobacco product. Abuse of prescription medicines is the cause the death for about 115 Americans daily. While substance abuse tendencies seem transmissible from one generation to next, human studies are challenging due to the long duration and confounding socio‐economic variables. Recent Food and Drug Administration guidance requires abuse liability testing in animals and humans for neuro-active medicines. However, there is no requirement for testing intergenerational transfer of abuse potential. Based on the similarities in nervous system development between mammalian embryos and regenerating planaria, we hypothesized that regenerating offspring of brown planaria parents exposed to substances of abuse (nicotine or ethanol) will demonstrate conditioned place preference similar to parent planaria, making them an alternative model for testing intergenerational transfer of substance abuse potential. Parent brown planaria exposed to nicotine or ethanol showed CPP in a concentration and time-dependent manner. We also demonstrated that regenerating brown planaria offspring are more sensitive than parents to CPP by nicotine or ethanol. In addition, exposure of parent planaria to nicotine or alcohol resulted in CPP in the regenerated offspring, without direct exposure to nicotine or ethanol during regeneration. Based on these results, regenerating brown planaria is a promising alternative model for testing intergenerational transfer of substance abuse potential.