Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring

ABSTRACT: BACKGROUND: A growing body of preclinical studies report that parental exposures can impact the behavior and physiology of offspring. Despite the prevalence of opioid exposure throughout human populations, little is known about the impact of paternal (male-line) opioid use on progeny; METHODS: Adult male rats self-administered morphine or saline for 60 days. These sires were then bred to drug-naïve dams to produce first-generation (F1) offspring. Morphine, cocaine, and nicotine self-administration were evaluated in adult F1 progeny. Molecular correlates of addiction-like behaviors in reward-related brain regions were also measured in a cohort of drug-naïve F1 offspring; RESULTS: Male offspring bred from morphine-exposed sires exhibited a dose-dependent increase in morphine self-administration and increased motivation to earn morphine infusions under a progressive ratio schedule of reinforcement. This phenotype was drug-specific, as self-administration of cocaine, nicotine, and sucrose were not altered by paternal morphine history. Accompanying these behavioral changes, increased mu-opioid receptor expression was observed in the ventral tegmental area (VTA), but not the nucleus accumbens (NAc), of male F1 offspring bred from morphine-exposed sires. RNA sequencing further revealed broad transcriptomic alterations to the F1 NAc and VTA transcriptomes; CONCLUSIONS: Paternal morphine exposure increased morphine addiction-like behavioral vulnerability in male progeny. This phenotype may be driven by adaptations to brain regions that modulate reward processing.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE328531 | GEO | 2026/05/01

REPOSITORIES: GEO