Fig. 3.

β₁-adrenergic signaling is required during and after context exposure for long-term extinction. All mice were conditioned on day 0 and exposed to context S for 5 min on day 1. Results shown are for testing in context S on day 2 with retrieval intact. (A) Effect of blocking β_1,2 signaling in control Dbh^+/- mice before (-0.5 h) or beginning 0–8 h after context S exposure. The main effect of treatment (P < 0.001) and interaction of treatment by time (P < 0.01) were significant. Prop blocked long-term extinction when given 0–3 h after context exposure, indicating a role for β₁-adrenergic signaling in the consolidation of extinction (see text for analogous results with CGP). Sal given 1–4 h after context exposure slightly increased freezing on day 2, possibly due to a small nonspecific disruption of extinction consolidation. (B) Stimulation of β₁ receptors in Dbh^-/- mice beginning shortly after context exposure does not rescue extinction. Xam was given before (-1 h) or immediately after context exposure (0 h and 0 + 3 h, with a second injection at 3 h for the latter group). The main effect of treatment (P < 0.02) and interaction of treatment by time (P < 0.01) were significant. (C) CNS restoration of NE in Dbh^-/- mice beginning shortly after context exposure does not rescue extinction (P > 0.5). Mice were given vehicle (Veh) or 1 g/kg L-DOPS plus 50 mg/kg benserazide (DOPS) immediately after context exposure. (D) The rescue of extinction by stimulation of β₁ receptors before context exposure in Dbh^-/- mice depends on stimulation of β₁ receptors 3 h after exposure. Mice were treated with Xam 1 h before context exposure and either Sal or Prop 3 h after exposure. For all graphs, retrieval on day 2 was facilitated by giving Sal/Xam-treated mice Xam 1 h before testing and by giving Veh/DOPS-treated mice 1 g/kg L-DOPS plus 50 mg/kg benserazide 5 h before testing. Significance comparing treatments within time: ^, P < 0.01; #, P < 0.001. Data were analyzed by ANOVA with treatment and time as factors.