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.
Highlights
Norepinephrine (NE) has long been implicated in fear and anxiety (Gray, 1978; Aston-Jones and Bloom, 1981; Aston-Jones et al, 1999, 2000; Sullivan et al, 1999; McGaugh et al, 2002), and is known to play a role in learning, memory and plasticity (Bailey et al, 2000; McGaugh et al, 2002; Roozendaal et al, 2004; Tully et al, 2007)
The differences between the paradigms are due to the fact that in auditory fear conditioning memory is consolidated in the amygdala (Schafe et al, 1999; Schafe and LeDoux, 2000; Rodrigues et al, 2004), whereas inhibitory avoidance (IA) memory formation is hippocampal dependent (O’Keefe and Nadel, 1978) with the amygdala modulating hippocampal learning and storage (McGaugh, 2000)
The results suggest that βARs in the LA are involved in the acquisition, but not the consolidation or expression, of memory for auditory fear conditioning
Summary
Norepinephrine (NE) has long been implicated in fear and anxiety (Gray, 1978; Aston-Jones and Bloom, 1981; Aston-Jones et al, 1999, 2000; Sullivan et al, 1999; McGaugh et al, 2002), and is known to play a role in learning, memory and plasticity (Bailey et al, 2000; McGaugh et al, 2002; Roozendaal et al, 2004; Tully et al, 2007). There have been many studies of NE contributions to aversive memory tasks, especially inhibitory avoidance (IA) (McGaugh, 2004; Roozendaal et al, 2008) These studies clearly show that NE, acting via beta-adrenergic receptors (βARs), contributes to the consolidation of long-term memory (LTM) of IA. Studies of auditory fear conditioning have failed to find effects of immediate post-training treatment with NE or the βAR antagonist propranolol given systemically (Lee et al, 2001), and post-training infusions of propranolol into in the LA and B fail to have an effect on LTM (Debiec and LeDoux, 2004) This discrepancy between results in IA and fear conditioning tasks is not restricted to NE manipulations It is not possible to use findings from IA tasks to explain the role of NE in the formation of memory for amygdala-dependent fear conditioning
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