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. 2011 Sep;18(9):598–604. doi: 10.1101/lm.2302811

Figure 1.

Figure 1.

Xamoterol impairs hippocampus-dependent memory. (A) Mice were fear conditioned and 1 d later vehicle or xamoterol was administered subcutaneously 30 min before testing contextual fear. Xamoterol caused a U-shaped, dose-dependent reduction in freezing that was maximal at 6 mg/kg. There were 5 mice per group except at 0 and 3 (11 and 10). F(5,35) = 10.1 and P < 0.0001 for the main effect of dose. (B) Mice were fear conditioned and 1 d later vehicle or xamoterol (Xam) was administered subcutaneously 30 min before testing cued fear. Xamoterol did not affect freezing before (Pre-CS) or during the tone used for training (conditioned stimulus = CS), indicating that xamoterol does not alter fear or freezing per se. There were 8 and 5 mice per group for vehicle and xamoterol. F(1,24) = 48 and P < 0.0001 for the main effect of tone; the main effect of drug and the interaction were not significant. (C) Xamoterol (6 mg/kg) impaired freezing when combined (X/N) with 3 mg/kg of the peripheral β receptor antagonist nadolol (Nad), indicating that xamoterol acts centrally to impair retrieval. F(1,28) = 48 and P < 0.0001 for the main effect of xamoterol; the main effect of nadolol (P = 0.1) and the interaction were not significant, although there was a trend for nadolol to increase freezing slightly in both groups. (D) Bilateral cannulae targeting the DH were implanted in mice. One week later, the mice were fear conditioned, and on the following day they were tested for contextual fear. DH infusions were performed 15 min before testing, with xamoterol causing impairment at 10 and 15 µg/DH. There were 5 and 6 mice per group for 0 and 10 and 5 and 15 µg/DH groups, respectively. F(3,18) = 3.65 and P = 0.032 for the main effect of dose. (E) Mice were fear conditioned, and 1 d later vehicle or xamoterol was infused into the DH 15 min before testing cued fear. Xamoterol did not affect freezing before or during the CS, indicating that DH infusion also does not alter fear or freezing. There were 5 mice per group. F(1,16) = 269 and P < 0.0001 for the main effect of tone. (* = P < 0.05, ∧ = P < 0.01, and # = P < 0.001 for post-hoc comparisons.)