Transgenerational attenuation of opioid self-administration as a consequence of adolescent morphine exposure

Fair M. Vassoler, David J. Oliver, Cristina Wyse, Ashley Blau, Michael Shtutman, Jill R. Turner, Elizabeth M. Byrnes

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The United States is in the midst of an opiate epidemic, with abuse of prescription and illegal opioids increasing steadily over the past decade. While it is clear that there is a genetic component to opioid addiction, there is a significant portion of heritability that cannot be explained by genetics alone. The current study was designed to test the hypothesis that maternal exposure to opioids prior to pregnancy alters abuse liability in subsequent generations. Female adolescent Sprague Dawley rats were administered morphine at increasing doses (5–25 mg/kg, s.c.) or saline for 10 days (P30-39). During adulthood, animals were bred with drug-naïve colony males. Male and female adult offspring (F1 animals) were tested for morphine self-administration acquisition, progressive ratio, extinction, and reinstatement at three doses of morphine (0.25, 0.75, 1.25 mg/kg/infusion). Grandoffspring (F2 animals, from the maternal line) were also examined. Additionally, gene expression changes within the nucleus accumbens were examined with RNA deep sequencing (PacBio) and qPCR. There were dose- and sex-dependent effects on all phases of the self-administration paradigm that indicate decreased morphine reinforcement and attenuated relapse-like behavior. Additionally, genes related to synaptic plasticity, as well as myelin basic protein (MBP), were dysregulated. Some, but not all, effects persisted into the subsequent (F2) generation. The results demonstrate that even limited opioid exposure during adolescence can have lasting effects across multiple generations, which has implications for mechanisms of the transmission of drug abuse liability in humans.

Original languageEnglish
Pages (from-to)271-280
Number of pages10
JournalNeuropharmacology
Volume113
DOIs
StatePublished - Feb 1 2017

Bibliographical note

Funding Information:
This work was generously supported by grants from the National Institutes of Health R01 DA025674 , R03 DA034886 and the Tufts University Provost Office Tufts Collaborates Award . The authors have no financial disclosures and declare no conflict of interest.

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • Epigenetic
  • Myelin basic protein
  • Opiate
  • RNA sequencing
  • Self-administration
  • Transgenerational

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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