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. 2021 Jan 28;11:2567. doi: 10.1038/s41598-021-82206-3

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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Rats exposed to long-access, but not short-access, oxycodone SA escalate their drug intake. (A) Experimental timeline of oxycodone self-administration (SA) training. Rats self-administered oxycodone using either short-access (ShA) (n = 10) (trained for 3 h for 20 days) or long-access (LgA) (n = 21–23) (trained for 3 h for 1–5 days, 6 h for 6–10 days, then 9 h for 11–20 days) paradigms. (B) LgA rats escalate their intake of oxycodone after the first 5 days of SA training. (C) LgA rats show significant increases in active lever presses during SA training. (D) LgA-H rats show two distinct intake phenotypes, high (LgA-H) (n = 10) and low (LgA-L) (n = 13) oxycodone takers, during the escalation phase. (E) LgA-H rats took substantially more oxycodone than LgA-L and ShA rats. Key to statistics: *, **, *** = p < 0.05, 0.01, 0.001, respectively, in comparison to Sal rats; #, ##, ### = p < 0.05, 0.01, 0.001, respectively, in comparison to SHA rats; $$, $$$ = p < 0.01, 0.001 in comparison to LgA-L rats. Stats were performed by either one-way or two-way ANOVA followed by Bonferroni or Fisher’s PLSD post hoc test.