Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour

Qiumin Le, Biao Yan, Xiangchen Yu, Yanqing Li, Haikun Song, Huiwen Zhu, Weiqing Hou, Dingailu Ma, Feizhen Wu, Yuqing Zhou and Lan Ma ()
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Qiumin Le: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University
Biao Yan: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University
Xiangchen Yu: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University
Yanqing Li: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University
Haikun Song: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University
Huiwen Zhu: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University
Weiqing Hou: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University
Dingailu Ma: Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University
Feizhen Wu: Laboratory of Epigenetics, Institutes of Biomedical Sciences, Fudan University
Yuqing Zhou: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University
Lan Ma: and Institute of Translational Neuroscience, Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Liability to develop drug addiction is heritable, but the precise contribution of non-Mendelian factors is not well understood. Here we separate male rats into addiction-like and non-addiction-like groups, based on their incentive motivation to seek cocaine. We find that the high incentive responding of the F0 generation could be transmitted to F1 and F2 generations. Moreover, the inheritance of high incentive response to cocaine is contingent on high motivation, as it is elicited by voluntary cocaine administration, but not high intake of cocaine itself. We also find DNA methylation differences between sperm of addiction-like and non-addiction-like groups that were maintained from F0 to F1, providing an epigenetic link to transcriptomic changes of addiction-related signalling pathways in the nucleus accumbens of offspring. Our data suggest that highly motivated drug seeking experience may increase vulnerability and/or reduce resistance to drug addiction in descendants.

Date: 2017
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DOI: 10.1038/ncomms15527

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