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. 2020 Apr 2;11:1635. doi: 10.1038/s41467-020-15423-5

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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. 3 — a Mice were injected bilaterally in the pre-frontal cortex with control (CTL) or lentivirus-Gpr56 constructs, as well as with CTL or lentivirus-sh-Gpr56 (inhibitor) constructs. b Overexpression of Gpr56 (n = 15) was associated with lower immobility time in the TST in comparison to control animals (n = 12), two-sided t = 3.07, p = 0.005. c Downregulation of Gpr56 (n = 8) produced increased immobility time, i.e. depressive-like behavior in the tail suspension test (TST) in comparison to control animals (n = 11), two-sided t = 2.203, p = 0.048. d Fluoxetine decreased immobility in control animals (n = 5), while this effect was strongly attenuated in sh-Gpr56-virus infused animals (n = 6); two-way ANOVA for repeated measures; treatment × group interaction F(1,9) = 6.80, p = 0.028; main effects for group F (1,9) = 25.4, p = 0.001 (as compared to control) and for treatment F(1,9) = 6.80 p = 0.001 (as compared to vehicle). e GPR56 agonist P7 has antidepressant-like effects. GPR56 agonist P7 peptide infused bilaterally with escalating doses in PFC decreases immobility time and demonstrates antidepressant-like effects, ANOVA F(1,4) = 4.88 p = 0.008. In comparison to vehicle (n = 13), both 1 mM (n = 7) and 2 mM (n = 4) doses demonstrate a significant decrease of immobility time (p < 0.01 and p = 0.01 respectively, two-sided post hoc test). Bars represent mean. Error bars represent standard error of the mean. **p < 0.01, *p < 0.05. Source data are provided as a Source Data file.