ArticleScientific reports2026
Methylphenidate exposure alters brain gene expression and induces transgenerational DNA methylation changes in Poecilia reticulata guppies.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Chronic exposure to stimulants is known to affect behavioral phenotypes and epigenetic profiles intergenerationally. We have previously shown that chronic methylphenidate hydrochloride (MPH) exposure in male guppies (Poecilia reticulata) induces persistent, paternally transmitted behavioral changes across multiple unexposed generations. Here, we investigated the underlying epigenetic signatures of this transgenerational behavioral inheritance. Building on our previous study, which used composite behavioral scores, we investigated the transgenerational inheritance patterns of individual behaviors and found a robust, male-lineage-dependent increase in swimming across unexposed G2-G4 female offspring. Our molecular analysis showed that chronic MPH exposure in G1 males alters brain gene expression, with 76 differentially expressed genes including genes with developmental and locomotory functions, and an over-representation of long non-coding RNAs. Furthermore, we found that unexposed G4 descendants from MPH-treated lineages exhibit widespread changes in brain DNA methylation, including genes related to developmental and swimming behavior. Interestingly, we found one lncRNA, LOC103476631, to be both differentially expressed in G1 males and differentially methylated in G4 fish, providing a compelling candidate for ncRNA-directed DNA methylation as a mechanism for the observed transgenerational epigenetic inheritance of swimming behavior.
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