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Title: Epigenetic effects of paternal cocaine on reward stimulus behavior and accumbens gene expression in mice

Abstract

Paternal cocaine use causes phenotypic alterations in offspring behavior and associated neural processing. In rodents, changes in first generation (F1) offspring include drug reward behavior, circadian timing, and anxiety responses. This study, utilizing a murine (C57BL/6J) oral cocaine model, examines the effects of paternal cocaine exposure on fundamental characteristics of offspring reward responses, including: 1) the extent of cocaine-induced effects after different durations of sire drug withdrawal; 2) sex- and drug-dependent differences in F1 reward preference; 3) effects on second generation (F2) cocaine preference; and 4) corresponding changes in reward area (nucleus accumbens) mRNA expression. We demonstrate that paternal cocaine intake over a single ˜40-day spermatogenic cycle significantly decreased cocaine (but not ethanol or sucrose) preference in a sex-specific manner in F1 mice from sires mated 24h after drug withdrawal. However, F1 offspring of sires bred 4 months after withdrawal did not exhibit altered cocaine preference. Altered cocaine preference also was not observed in F2's. RNASeq analyses of F1 accumbens tissue revealed changes in gene expression in male offspring of cocaine-exposed sires, including many genes not previously linked to cocaine addiction. Enrichment analyses highlight genes linked to CNS development, synaptic signaling, extracellular matrix, and immune function. Expression correlation analyses identifiedmore » a novel target, Fam19a4, that may negatively regulate many genes in the accumbens, including genes already identified in addiction. Collectively, these results reveal that paternal cocaine effects in F1 offspring may involve temporally limited epigenetic germline effects and identify new genetic targets for addiction research.« less

Authors:
 [1];  [2];  [2]; ORCiD logo [2]; ORCiD logo [2];  [1]
  1. Kent State Univ., Kent, OH (United States)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1559673
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Behavioural Brain Research
Additional Journal Information:
Journal Volume: 367; Journal Issue: N/A
Publisher:
ELSEVIER
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Yaw, Alexandra M., Prosser, Rebecca, Jones, Piet C., Garcia, Benjamin J., Jacobson, Daniel A., and Glass, J David. Epigenetic effects of paternal cocaine on reward stimulus behavior and accumbens gene expression in mice. United States: N. p., 2019. Web. doi:10.1016/j.bbr.2019.02.043.
Yaw, Alexandra M., Prosser, Rebecca, Jones, Piet C., Garcia, Benjamin J., Jacobson, Daniel A., & Glass, J David. Epigenetic effects of paternal cocaine on reward stimulus behavior and accumbens gene expression in mice. United States. doi:10.1016/j.bbr.2019.02.043.
Yaw, Alexandra M., Prosser, Rebecca, Jones, Piet C., Garcia, Benjamin J., Jacobson, Daniel A., and Glass, J David. Mon . "Epigenetic effects of paternal cocaine on reward stimulus behavior and accumbens gene expression in mice". United States. doi:10.1016/j.bbr.2019.02.043.
@article{osti_1559673,
title = {Epigenetic effects of paternal cocaine on reward stimulus behavior and accumbens gene expression in mice},
author = {Yaw, Alexandra M. and Prosser, Rebecca and Jones, Piet C. and Garcia, Benjamin J. and Jacobson, Daniel A. and Glass, J David},
abstractNote = {Paternal cocaine use causes phenotypic alterations in offspring behavior and associated neural processing. In rodents, changes in first generation (F1) offspring include drug reward behavior, circadian timing, and anxiety responses. This study, utilizing a murine (C57BL/6J) oral cocaine model, examines the effects of paternal cocaine exposure on fundamental characteristics of offspring reward responses, including: 1) the extent of cocaine-induced effects after different durations of sire drug withdrawal; 2) sex- and drug-dependent differences in F1 reward preference; 3) effects on second generation (F2) cocaine preference; and 4) corresponding changes in reward area (nucleus accumbens) mRNA expression. We demonstrate that paternal cocaine intake over a single ˜40-day spermatogenic cycle significantly decreased cocaine (but not ethanol or sucrose) preference in a sex-specific manner in F1 mice from sires mated 24h after drug withdrawal. However, F1 offspring of sires bred 4 months after withdrawal did not exhibit altered cocaine preference. Altered cocaine preference also was not observed in F2's. RNASeq analyses of F1 accumbens tissue revealed changes in gene expression in male offspring of cocaine-exposed sires, including many genes not previously linked to cocaine addiction. Enrichment analyses highlight genes linked to CNS development, synaptic signaling, extracellular matrix, and immune function. Expression correlation analyses identified a novel target, Fam19a4, that may negatively regulate many genes in the accumbens, including genes already identified in addiction. Collectively, these results reveal that paternal cocaine effects in F1 offspring may involve temporally limited epigenetic germline effects and identify new genetic targets for addiction research.},
doi = {10.1016/j.bbr.2019.02.043},
journal = {Behavioural Brain Research},
number = N/A,
volume = 367,
place = {United States},
year = {2019},
month = {7}
}

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Works referencing / citing this record:

The epigenetic legacy of illicit drugs: developmental exposures and late-life phenotypes
journal, October 2019

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