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Establishment of Multi-stage Intravenous Self-administration Paradigms in Mice

Publication ,  Journal Article
Slosky, LM; Pires, A; Bai, Y; Clark, N; Hauser, ER; Gross, JD; Porkka, F; Zhou, Y; Chen, X; Pogorelov, VM; Toth, K; Wetsel, WC; Barak, LS; Caron, MG
November 27, 2020

A genetically tractable animal model would provide a needed strategy to resolve the biological basis of drug addiction. Intravenous self-administration (IVSA) is the gold standard for modeling cocaine and opioid addiction in animals, but technical limitations have precluded the widespread use of IVSA in mice. Here, we describe the first IVSA paradigms for mice that capture the multi-stage nature of the disease and permit predictive modeling. Mice with long-standing indwelling jugular catheters engaged in cocaine or opioid-associated lever responding that was fixed ratio- and dose-dependent, extinguished by the withholding of drug, and reinstated by the presentation of paired cues. Machine learning revealed that vulnerability to drug seeking and relapse were predicted by a mouse’sresponse to novelty, sensitivity to drug-induced locomotion, and drug-taking behavior. Application of this behavioral and analysis approach to genetically-engineered mice will facilitate the identification of the neural circuits driving addiction susceptibility and relapse and focused therapeutic development.

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Publication Date

November 27, 2020
 

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Slosky, L. M., Pires, A., Bai, Y., Clark, N., Hauser, E. R., Gross, J. D., … Caron, M. G. (2020). Establishment of Multi-stage Intravenous Self-administration Paradigms in Mice. https://doi.org/10.1101/2020.11.25.398503
Slosky, Lauren M., Andrea Pires, Yushi Bai, Nicholas Clark, Elizabeth R. Hauser, Joshua D. Gross, Fiona Porkka, et al. “Establishment of Multi-stage Intravenous Self-administration Paradigms in Mice,” November 27, 2020. https://doi.org/10.1101/2020.11.25.398503.
Slosky LM, Pires A, Bai Y, Clark N, Hauser ER, Gross JD, et al. Establishment of Multi-stage Intravenous Self-administration Paradigms in Mice. 2020 Nov 27;
Slosky, Lauren M., et al. Establishment of Multi-stage Intravenous Self-administration Paradigms in Mice. Nov. 2020. Crossref, doi:10.1101/2020.11.25.398503.
Slosky LM, Pires A, Bai Y, Clark N, Hauser ER, Gross JD, Porkka F, Zhou Y, Chen X, Pogorelov VM, Toth K, Wetsel WC, Barak LS, Caron MG. Establishment of Multi-stage Intravenous Self-administration Paradigms in Mice. 2020 Nov 27;

DOI

Publication Date

November 27, 2020