Figure 5. Development of depression-like behaviors is interrupted when pain is controlled. A, Timeline of behavioral tests with acute administration of GBP. B–D, Timeline of behavioral tests with chronic administration of GBP. The time course for the onset of analgesia by GBP (100 mg/kg, i.p.) in SNI animals is shown for pin (C; one-way RM-ANOVA followed by Dunnett's test, F(1.464, 13.17) = 25.45, p < 0.0001, **p < 0.01, ***p < 0.001 vs baseline at 0 min) and von Frey test (D; n = 10 rats; one-way RM-ANOVA followed by Dunnett's test, F(1.274, 11.47) = 14.83, p = 0.0016, *p < 0.05, **p < 0.01 vs baseline at 0 min). E, F, Chronic perfusion of GBP with implanted osmotic pumps for 16 h can also reduce hypersensitivity to pin (E; t(9) = 6.03, p = 0.0002, paired t test) and von Frey test (F; t(9) = 3.25, **p = 0.01 by the paired t test). G–J, Chronic administration of GBP in the cage water bottle also reduces hypersensitivity to the pin (G) and von Frey test (H; two-way RM-ANOVA followed by Dunnett's test, F(18,186) = 11.93, p < 0.0001 for pin test; F(18,186) = 6.279, p < 0.0001 for von Frey test, *p < 0.05, **p < 0.01, ***p < 0.001), and AUC analysis for the pin test (I) and von Frey test (J; two-way ANOVA followed by Dunnett's test, F(1,31) = 17.00, p < 0.0001 for pin test; F(1,31) = 25.00, p < 0.0001 for von Frey test, ***p < 0.001). K, Acute administration of GBP has no effects on SPT, and chronic GBP blocks development of reduced sucrose preference by injury (two-way ANOVA followed by the Sidak test, F(1,46) = 17.16, p = 0.0001 *p = 0.017, ***p < 0.001). L, Acute administration of GBP showed no effects on NSF, and chronic GBP reversed development of NSF (two-way ANOVA followed by the Sidak test, F(1,46) = 15.4 between with and without SNI, p = 0.0003, **p = 0.002, ***p < 0.001). M, Acute administration of GBP has no effect on FST, and chronic GBP reversed development of FST after neuropathic pain (two-way ANOVA followed by the Sidak test, F(1,46) = 9.086 between with and without SNI, p = 0.0042, *p = 0.029 between Sham+saline and SNI+saline, p = 0.019 between Sham+acute GBP and SNI+acute GBP). N, GBP can improve impaired motor activity in OFT (two-way ANOVA followed by the Sidak test, F(2,47) = 5.63 between with and without SNI, p = 0.0064, *p = 0.047 between with and without SNI). O, GBP didn't have effects on the time spent in the center. Data are presented as mean ± SD.