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Sex-specific disruption of VTA transcriptome at acute vs. extended morphine abstinence timepoints

ABSTRACT: Incubation of craving is a phenomenon characterized by the progressive augmentation of drug craving over a period of extended abstinence. Gene expression analyses can be leveraged to define transcriptomic changes associated with neural adaptions occurring during abstinence, informing understanding of mechanisms underlying craving and relapse. Previously, we identified differential disruptions to the nucleus accumbens transcriptome between acute and extended morphine abstinence timepoints in a rat model. Here, we expand this work to further test effects of morphine abstinence on gene expression in the ventral tegmental area (VTA), in both females and males. We additionally compare small RNA expression from plasma exosomes collected from a separate cohort of heroin-exposed males at the same acute and extended abstinence timepoints. Alterations to the VTA transcriptome diverged significantly between abstinence timepoints and sexes; specifically, VTA gene expression was altered at the acute abstinence timepoint in both sexes, but at the extended abstinence timepoint only in females, contrasting our previous findings in NAc. In heroin-abstinent males, exosomal small RNA was also altered exclusively during acute abstinence. This research expands understanding of VTA-specific regulation of abstinence and craving, in addition to identifying candidate systemic biomarkers for opioid exposure.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE335708 | GEO | 2026/07/01

REPOSITORIES: GEO

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