Time course of depressive-like behaviors and σ₁R expression, and effect of SA4503 treatment on depressive-like behaviors in TAC mice.

<p>A: Immobility time in a forced swimming test was measured 2, 4 and 6 weeks after TAC surgery. B: Immobility time in a tail suspension test was similarly measured. Groups consisted of 6–8 mice. C: Western blot analysis of σ₁R and β-tubulin (as a loading control) proteins in the CA1 region, dentate gyrus (DG) and medial prefrontal cortex (mPFC) of sham and TAC mice. Immunoblotting with anti-β-tubulin antibody indicates equal protein loading. D: Densitometric quantification of σ₁R immunoreactivity (n = 6). Columns represent means ± S.E.M. <i>F</i>(3, 20) = 4.875, <i>P</i><0.05 (CA1); <i>F</i>(3, 20) = 6.182, <i>P</i><0.01 (DG); <i>F</i>(3, 20) = 0.698, <i>P</i> = 0.564 (mPFC). *, <i>P</i><0.05 and **, <i>P</i><0.01 versus sham-operated mice. E: Immobility time in a forced swimming test was measured 6 weeks after TAC surgery with or without drug treatment for the last 4 weeks. F: Immobility time in a tail suspension test was similarly measured. TAC mice were treated with SA4503 (0.1, 0.5 or 1.0 mg/kg) or SA4503 (1.0 mg/kg) plus NE-100 (1.0 mg/kg), as indicated (n = 6). <i>F</i>(5, 37) = 20.740, <i>P</i><0.01 (forced swimming); <i>F</i>(5, 38) = 2.692, <i>P</i><0.05 (tail suspension). G: Consumption of normal water and 1% sucrose solution was measured in continuous 5 days. Sucrose preference (%) was calculated as ratio of 1% sucrose solution consumption to total consumption. TAC mice were treated with SA4503 (1.0 mg/kg) or SA4503 (1.0 mg/kg) plus NE-100 (1.0 mg/kg), as indicated (n = 6). Columns represent means ± S.E.M. *, <i>P</i><0.05 and **, <i>P</i><0.01 versus the sham group; ##, <i>P</i><0.01 versus the TAC/vehicle treated group; <b>††</b>, <i>P</i><0.01 versus the TAC plus SA4503 (1 mg/kg)-treated group.