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. 2020 Oct 2;10:336. doi: 10.1038/s41398-020-01014-x

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© The Author(s) 2020

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. 2 — a D2R agonist quinpirole (0.5 mg/kg, i.p.)-induced open-field activity, in AAV-Cre-GFP or AAV-GFP-injected mTOR^flox/flox mice and WT control mice. Data are mean ± SEM, repeated measures two-way ANOVA followed by Bonferroni post-hoc test. b Catalepsy (as measured by time on the bar)-induced by D2R antagonist haloperidol (0.5 mg/kg, i.p.) in AAV-Cre-GFP or AAV-GFP-injected mTOR^flox/flox and WT control mice. Data are mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001, repeated measures two-way ANOVA followed by Bonferroni post-hoc test. c Representative image of AAV-Cre-GFP or AAV-GFP-injected mTOR^flox/flox mice treated with haloperidol (180 min). mTOR^flox/flox mice injected with AAV-GFP (n = 13, female = 10, male = 3), AAV-Cre-GFP (n = 13, female = 6, male = 7) or WT mice injected with AAV-GFP or AAV-Cre-GFP (n = 11, female = 5, male = 6) were treated with vehicle or drug (a–c). d Western blot analysis of indicated proteins from striatum of indicated mice after 20 min of haloperidol (0.5 mg/kg, i.p.) or saline injection. e Bar graph indicates quantification of the indicated proteins from (d). Data are mean ± SEM, n = 4 for saline injected group and n = 5 for haloperidol treated group, *P < 0.05, **P < 0.01, ***P < 0.001, two-way ANOVA, Bonferroni post-hoc test. f, g Quantification of catalepsy induced by D2R antagonist haloperidol (0.5 mg/kg, i.p.) in vehicle or pretreated with rapamycin (5 mg/kg, i.p.) for 20 min (f) or 3 hr (g) in C57BL/6 WT mice. Data are mean ± SEM, n = 5 per group, ***P < 0.001, repeated measures two-way ANOVA, Bonferroni post-hoc test. h Representative image of haloperidol-induced catalepsy in WT mice pretreated with rapamycin or vehicle. i, j Western blot analysis (i) and quantification (j) of indicated targets from the striatal tissue after 20 min of haloperidol and rapamycin pretreatment (3 hr). Data are mean ± SEM, n = 5 per group, *P < 0.05, **P < 0.01, ***P < 0.001, two-way ANOVA, Bonferroni post-hoc test. k Model shows mTOR mediates D2R inhibitory signals to induce catalepsy linked to extrapyramidal side effects in humans.