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. 2022 Jul 15;5:709. doi: 10.1038/s42003-022-03667-4

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© The Author(s) 2022

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a PND16 male mice were injected with an anesthetic dose of ketamine for 5 consecutive days. The duration of ketamine anesthesia, measured as the LOR reflex duration, was significantly reduced by repeated injections (acute tolerance) (p = 0.001, repeated measures [RM]-ANOVA; n = 12). b Normal weight gain in mice that received repetitive ketamine anesthesia (p = 0.115, RM-ANOVA; Control, n = 15; Anesthesia, n = 12). c–g Early repeated ketamine anesthesia does not affect the development of behavioral sensitization to low-dose ketamine. c, d Schematic diagram of the experimental design. A behavioral sensitization test was performed 1 week after anesthesia injections. e Early ketamine anesthesia did not affect baseline activity at PND28 (p = 0.158, Student’s t test; Control-Saline, n = 12; Anesthesia Saline, n = 11). f Behavioral sensitization to repeated low-dose ketamine developed in both groups (one-way ANOVA with Tukey multiple comparisons; Control-Ketamine, n = 12; anesthesia ketamine, n = 12). g The development of behavioral sensitization was comparable between the two groups (p = 0.583, RM-ANOVA; Control-Ketamine, n = 12; Anesthesia ketamine, n = 12). Values are presented as means ± SD (n.s., not significant; ***p < 0.001).