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. 2022 Jun 22;27(10):4009–4022. doi: 10.1038/s41380-022-01662-z

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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–E Changes in Notch1 signalling in the mPFC of METH-sensitized mice. A Procedure for generating the METH-induced locomotor sensitization model. B Representative mouse tracks from days 1, 7 and 23 were illustrated. C METH-induced locomotor sensitization in mice. One-way repeated-measures ANOVA revealed a significant main effect of METH [F _{(2, 21)} = 47.41, P < 0.001]. Subsequent post hoc LSD comparisons found significantly greater locomotor activity in the METH-sensitized group than in the saline group on day 1, day 7 and day 23. The METH-sensitized group showed a significant increase in locomotor activity compared with the METH-acute group on day 23 and itself on day 1. D The amount of time mice spent in the centre zone significantly decreased in the METH-sensitized group compared with the saline and acute METH group on day 23 [One-way repeated-measures ANOVA, F _{(2, 15)} = 3.66_, P < 0.05]. E Changes in the expression of Notch1 signalling pathway components following METH sensitization in the mPFC. There was significant downregulation of Notch1 [F _{(2, 17)} = 6.41, P < 0.01]_, Jagged1 [F _{(2, 15)} = 3.81, P < 0.05], RBP-J [F _{(2, 20)} = 18.05, P < 0.001], and Hes1 [F _{(2, 15)} = 29.68, P < 0.001] in both the METH-acute and METH_-sensitized groups by one-way ANOVA. F Representative images of immunofluorescence staining for Notch1 receptors in mPFC between the METH-sensitized group and the saline group. Quantitative analysis of Notch1-positive cells in the METH-sensitized group showed a significant decrease (t₂₆ = 9.76, ***P < 0.001) by student’s-t test (scale bar = 50 μm, n = 3 / group, 10–15 photos). G–K Intra-mPFC DAPT treatment attenuated METH-induced locomotor sensitization. G Procedure for the administration of DAPT in the mPFC in METH-induced sensitization mice. H Location of the DAPT and vehicle microinjection cannula tips in the mPFC. I Representative tracks of vehicle-METH and DAPT-METH mice on day 1 and day 23. J Intra-mPFC infusion of DAPT significantly attenuated the hyperlocomotion evoked by METH on day 1 and day 23. Mixed-design ANOVA with a LSD post hoc multiple comparison revealed significant main effects of DAPT [F _{(1, 21)} = 5.38, P < 0.05]; METH [F _{(1, 21)} = 206.21, P < 0.001]; but not DAPT×METH [F _{(1, 21)} = 1.36, P > 0.05]. K The time mice spent in the centre zone was higher in the DAPT-METH group than in the vehicle-METH group on day 23. Mixed-design ANOVA with LSD post hoc multiple comparisons show the main effect of DAPT [F _{(1, 20)} = 1.24, P > 0.05]; METH [F _{(1, 20)} = 0.74, P > 0.05] and DAPT × METH [F _{(1, 20)} = 6.45, P < 0.05]. *P < 0.05, **P < 0.01, ***P < 0.001 vs. paired saline group; ^P < 0.05 vs. paired METH group; #P < 0.05, ###P < 0.001 vs. same group on day 1. Data were presented as mean ± S.E.M, n = 6–8.