Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

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2019
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Golden, Sam A.
Jin, Michelle
Venniro, Marco
Michaelides, Michael
Shaham, Yavin
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We recently developed a mouse model of appetitive operant aggression and reported that adult male outbred CD-1 mice lever-press for the opportunity to attack subordinate male mice and relapse to aggression seeking during abstinence. Here we studied the role of nucleus accumbens (NAc) dopamine receptor (Drd)1- and Drd2-expressing neurons in aggression self-administration and aggression seeking. We trained CD-1 mice to self-administer intruders (9 d, 12 trials/d) and tested them for aggression self-administration and aggression seeking on abstinence Day 1. We used immunohistochemistry and in situ hybridization to measure the neuronal activity marker Fos in the NAc, and cell-type-specific colocalization of Fos with Drd1- and Drd2-expressing neurons. To test the causal role of Drd1- and Drd2-expressing neurons, we validated a transgenic hybrid breeding strategy crossing inbred Drd1-Cre and Drd2-Cre transgenic mice with outbred CD-1 mice and used cell-type-specific Cre-DREADD (hM4Di) to inhibit NAc Drd1- and Drd2-expressing neuron activity. We found that aggression self-administration and aggression seeking induced higher Fos expression in NAc shell than in core, that Fos colocalized with Drd1 and Drd2 in both subregions, and that chemogenetic inhibition of Drd1-, but not Drd2-, expressing neurons decreased aggression self-administration and aggression seeking. Results indicate a cell-type-specific role of Drd1-expressing neurons that is critical for both aggression self-administration and aggression seeking. Our study also validates a simple breeding strategy between outbred CD-1 mice and inbred C57-based Cre lines that can be used to study cell-type and circuit mechanisms of aggression reward and relapse.

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570 Biowissenschaften, Biologie
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accumbens, addiction, aggression, motivation, relapse, reward
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ISO 690GOLDEN, Sam A., Michelle JIN, Conor HEINS, Marco VENNIRO, Michael MICHAELIDES, Yavin SHAHAM, 2019. Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice. In: The Journal of Neuroscience. Society for Neuroscience. 2019, 39(13), pp. 2482-2496. ISSN 0270-6474. eISSN 1529-2401. Available under: doi: 10.1523/JNEUROSCI.2409-18.2019
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@article{Golden2019Nucle-51545,
  year={2019},
  doi={10.1523/JNEUROSCI.2409-18.2019},
  title={Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice},
  number={13},
  volume={39},
  issn={0270-6474},
  journal={The Journal of Neuroscience},
  pages={2482--2496},
  author={Golden, Sam A. and Jin, Michelle and Heins, Conor and Venniro, Marco and Michaelides, Michael and Shaham, Yavin}
}
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