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. 2022 Mar 23;19(2):592–607. doi: 10.1007/s13311-022-01215-w

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© The Author(s) 2022, corrected publication 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 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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Fig. 1 — SR8278 treatment recovered mood-related behavioral deficits shown in 6-OHDA-lesioned mice. (a) Experimental scheme of behavior tests. A single injection of 6-hydroxydopamine (6-OHDA) was administrated into the left dorsal striatum. After 5 weeks post injection, mood-related behavioral tests were carried out at the indicated time of day (circadian time [CT] 22–01 vs. CT10-13). The local injection of SR8278 (20 μg/mouse) into the midbrain was performed 3 h before each behavioral test. The image was used to confirm cannula placement in the VTA by TH staining to show DA neurons in the SN and VTA (inset). Scale bar = 500 μm. (b) Changes in depression-like behaviors after SR8278 microinfusion into the midbrain of VEH- and 6-OHDA-treated mice by a forced swim test (FST) and tail suspension test (TST) (FST: two-way ANOVA, p < 0.0001 for injection group, p < 0.0001 for time, p = 0.0021 for interaction) (TST: two-way ANOVA, p < 0.0001 for injection group, p = 0.0624 for time, p = 0.0105 for interaction). (c) Alternation of anxiety-like behaviors after SR8278 administration of VEH- and 6-OHDA-treated mice by an elevated plus maze test (EPM) (duration: two-way ANOVA, p = 0.0021 for injection group, p = 0.0025 for time, p = 0.0005 for interaction) (frequency: two-way ANOVA, p = 0.0240 for injection group, p < 0.0001 for time, p = 0.0182 for interaction) (distance traveled: two-way ANOVA, p = 0.5047 for injection group, p = 0.0013 for time, p = 0.6996 for interaction) (center crossings: two-way ANOVA, p = 0.9616 for injection group; p = 0.0245 for time; p = 0.8537 for interaction). Data are presented as mean ± SEM. Sample sizes (animals) are indicated by the numbers inside bars. Newman-keuls corrected post-hoc comparisons are indicated by *p < 0.05, **p < 0.01, ***p < 0.001 and ns, non-significant