Beta-adrenergic receptors in the lateral nucleus of the amygdala contribute to the acquisition but not the consolidation of auditory fear conditioning

Abstract

Beta-adrenergic receptors (βARs) have long been associated with fear disorders and with learning and memory. However, the contribution of these receptors to Pavlovian fear conditioning, a leading behavioral model for studying fear learning and memory, is still poorly understood. The aim of this study was to investigate the involvement of βAR activation in the acquisition, consolidation and expression of fear conditioning. We focused on manipulations of βARs in the lateral nucleus of the amygdala (LA) because of the well-established contribution of this area to fear conditioning. Specifically, we tested the effects of intra-LA microinfusions of the βAR antagonist, propranolol, on learning and memory for auditory Pavlovian fear conditioning in rats. Pre-training propranolol infusions disrupted the initial acquisition, short-term memory (STM), and long-term memory (LTM) for fear conditioning, but infusions immediately after training had no effect. Further, infusion of propranolol prior to testing fear responses did not affect fear memory expression. These findings indicate that amygdala βARs are important for the acquisition but not the consolidation of fear conditioning.

Keywords: acquisition; beta-adrenergic; consolidation; fear conditioning; lateral amygdala; norepinephrine.

Figure 1

Cannula placements in the lateral amygdala. Images show cannula placements for rats included in Experiments 1–5, as indicated. Symbols indicate injection sites from each of the three dose groups (°0 μg, ▲ 0.1 μg, •1 μg).

Figure 2

Post-training propranolol does not affect LTM for fear conditioning. Rats from Experiment 3 were given microinfusions of propranolol (0 μg, n = 5; 0.1 μg, n = 5; 1 μg, n = 5) into the lateral amygdala (LA) immediately after three-trial auditory fear conditioning. Post-training propranolol had no effect on long-term memory (LTM) for fear conditioning when tested drug-free 2 days later. The figure depicts mean freezing levels during the LTM test.

Figure 3

Pre-training propranolol disrupts LTM for fear conditioning. Rats from Experiment 1 were given microinfusions of propranolol (0 μg, n = 6; 0.1 μg, n = 6; 1 μg, n = 7) into the lateral amygdala (LA) prior to three-trial auditory fear conditioning. Propranolol pre-treated rats showed attenuated long-term memory (LTM) for fear conditioning when tested drug-free 2 days later. The figure depicts mean freezing levels during the LTM test. ** indicates significantly lower freezing relative to vehicle (p < 0.01).

Figure 4

Pre-training propranolol disrupts STM and LTM for fear conditioning. Rats from Experiment 2 were given microinfusions of propranolol (0 μg, n = 7; 0.1 μg, n = 6; 1 μg, n = 6) into the lateral amygdala (LA) prior to three-trial auditory fear conditioning. Propranolol pre-treated rats showed attenuated short-term memory (STM) when tested at three hours after fear conditioning, and memory was still impaired when tested for long-term memory (LTM) 2 days later. The figure depicts mean freezing levels during the STM and LTM tests. ** indicates significantly lower freezing relative to vehicle (p < 0.01).

Figure 5

Pre-training propranolol disrupts within-session fear acquisition. Propranolol pre-treated rats from Experiments 1 and 2 (0 μg, n = 13; 0.1 μg, n = 12; 1 μg, n = 13) showed impaired freezing to the auditory conditioned stimulus (CS) within the fear conditioning session. The figure depicts mean freezing levels during the second and third trials of the three-trial training session. ** indicates significantly lower freezing relative to vehicle (p = 0.01).

Figure 6

Pre-testing propranolol does not affect fear expression. Rats from Experiment 4 were fear conditioned, and then 2 days later given microinfusions of propranolol (0 μg, n = 5; 0.1 μg, n = 7; 1 μg, n = 6) into the lateral amygdala (LA) immediately before a fear memory test. Propranolol had no effect on fear memory expression. The figure depicts mean freezing levels during the expression test.