Fig. 1.
Manipulation of β1-adrenergic signaling affects both contextual memory retrieval and long-term extinction of contextual fear. Fear conditioning was performed on day 0 in the training apparatus (context S = shock). Context exposure was performed on day 1 for 5 min (without shock) either in context S (S, squares and diamonds) or a distinct context (N = neutral; circles). Some mice were not exposed on day 1 (triangles). Extinction was assessed on day 2 or 5 in context S. For A and B, control mice (+/- for Dbh+/-, filled symbols) were treated with Sal and NE/E-deficient mice (-/- for Dbh-/-, open symbols) were treated with the β1 agonist Xam (3 mg/kg) when testing intact retrieval (Ret) of contextual fear. Control mice were treated with the β1,2 antagonist Prop (1 mg/kg) or the β1 antagonist CGP (1 mg/kg), and Dbh-/- mice were treated with Sal when testing impaired retrieval (Block). Drug treatments (e.g., Prop/Sal) are for day 1/day 2, respectively. (A) When retrieval was intact during context exposure (day 1) and testing (day 2), extinction (low freezing) was apparent on day 2 for mice exposed to context S but not context N on day 1 (relative to mice not exposed on day 1). (B) When retrieval was impaired during context exposure, extinction was not observed on day 2. C and D demonstrate that contextual fear, its extinction, and the block of extinction last at least 5 d and that the latter is not due to state-dependent drug effects. State-dependent drug effects could be evaluated because contextual memory retrieval does not depend on adrenergic signaling 5 d or longer after conditioning. (C) When retrieval was intact during context exposure and testing, extinction was apparent on day 5 for mice exposed to context S on day 1. (D) When retrieval was impaired during context S exposure on day 1, extinction was not apparent on day 5. For all graphs, there were no significant differences by genotype under equivalent retrieval conditions. Data were analyzed by ANOVA with exposure context, genotype, treatment, and day as factors. For all figures, symbols indicate mean ± standard error, and there were 5–12 mice per group.