3.5.6. Water T-Maze

For the WTM (Figure 6e), a repeated measures ANOVA (shock × virus × drug × time; 2 × 2 × 2 × 2) revealed significant main effects of shock [F(1,56) = 117.663, *p* < 0.001], virus [F(1,56) = 25.030, *p* < 0.001], and drug [F(1,56) = 13.504, *p* < 0.01]. We also identified the following significant interactions: shock × virus [F(1,56) = 19.996, *p* < 0.001], shock × drug [F(1,56) = 6.823, *p* < 0.05], virus × drug [F(1,56) = 7.294, *p* < 0.01], and shock × virus × drug [F(1,56) = 6.368, *p* < 0.05]. Post hoc analysis revealed that in the acquisition and the reversal phases, fewer trials were needed to reach the criterion in the non-shocked groups (GFP + Veh, DR + Veh, DR + URB) compared with the shocked groups: Shock/GFP + Veh (acquisition, *p* < 0.01; reversal, *p* < 0.001), Shock/DR + Veh (acquisition, *p* < 0.001; reversal: *p* < 0.01) and Shock/DR + URB (acquisition, *p* < 0.001; reversal, *p* < 0.01). The Shock/GFP + URB group also demonstrated a decreased number of trials compared with the Shock/GFP + Veh group (acquisition, *p* < 0.001; reversal, *p* < 0.01) and the Shock/DR + URB group (acquisition: *p* < 0.001; reversal: *p* < 0.01). Hence, downregulating β-catenin in the NAc had no effect on WTM performance, but it did block the preventative effects of URB597 in shocked rats.

#### 3.5.7. Forced Swim Test

For the FST (Figure 6f), a three-way ANOVA on immobility revealed significant main effects of shock [F(1,56) = 283.367, *p* < 0.001], virus [F(1,56) = 23.916, *p* < 0.001], and drug [F(1,56) = 23.916, *p* < 0.001], as well as the following significant interactions: shock × virus [F(1,56) = 30.606, *p* < 0.001], shock × drug [F(1,56) = 23.423, *p* < 0.001], virus × drug [F(1,56) = 24.432, *p* < 0.001], and shock × virus × drug [F(1,56) = 17.059, *p* < 0.001]. Post hoc analysis revealed that the Shock/GFP + URB597 group demonstrated decreased immobility compared with the Shock/GFP + Veh and Shock/DR + URB597 (both *p* < 0.001) groups. In addition, an increase in immobility was observed in the other shocked groups (Shock/GFP + Veh, Shock/DR + URB597, and Shock/DR + Veh) compared to the non-shocked counterparts (NoShock/GFP + Veh, NoShock/DR + URB597, and NoShock/DR + Veh; all *p* < 0.001). Hence, downregulating β-catenin in the NAc blocked the preventive effects of URB597 on despair-like behavior in the FST in rats exposed to shock and reminders.

No significant differences were observed between the Shock/GFP + Veh and Shock/ DR + Veh groups, suggesting that downregulation had no effect on behavior by itself in shocked rats. In the non-shocked groups, we observed a difference between the NoShock/GFP + Veh and NoShock/DR + Veh groups in the social preference test, suggesting that downregulation decreased social preference.
