Type of Publication: | Journal article |
Publication status: | Published |
Author: | Golden, Sam A.; Jin, Michelle; Heins, Conor; Venniro, Marco; Michaelides, Michael; Shaham, Yavin |
Year of publication: | 2019 |
Published in: | The Journal of Neuroscience ; 39 (2019), 13. - pp. 2482-2496. - Society for Neuroscience. - ISSN 0270-6474. - eISSN 1529-2401 |
Pubmed ID: | 30655356 |
DOI (citable link): | https://dx.doi.org/10.1523/JNEUROSCI.2409-18.2019 |
Summary: |
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.
|
Subject (DDC): | 570 Biosciences, Biology |
Keywords: | accumbens, addiction, aggression, motivation, relapse, reward |
Refereed: | Yes |
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GOLDEN, 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. 39(13), pp. 2482-2496. ISSN 0270-6474. eISSN 1529-2401. Available under: doi: 10.1523/JNEUROSCI.2409-18.2019
@article{Golden2019Nucle-51545, title={Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice}, year={2019}, doi={10.1523/JNEUROSCI.2409-18.2019}, 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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