Post-Training Intra-Basolateral Amygdala Infusions of Norepinephrine Enhance Consolidation of Memory for Contextual Fear Conditioning

Abstract

Post-training infusions of drugs, including noradrenergic agonists and antagonists, into the basolateral amygdala (BLA) influence the consolidation of memory for training in several tasks, including inhibitory avoidance. There is, however, conflicting evidence concerning whether post-training intra-BLA drug infusions modulate the consolidation of contextual fear conditioning (CFC). In the present study, norepinephrine (NE) was infused bilaterally into the BLA of male Sprague Dawley rats immediately after training on two CFC tasks: a Y-maze and a straight alley. Post-training intra-BLA infusions enhanced memory of CFC training in the Y-maze, as assessed by percentage of time spent freezing and shock arm entrance latencies. Post-training intra-BLA infusions of NE enhanced 48 hr retention of CFC training in the straight alley, as assessed by shock compartment entrance latencies and the number of shocks required to learn to avoid entering the shock compartment. These findings indicate that the consolidation of memory for CFC, like that for inhibitory avoidance training, is influenced by post-training neuromodulatory influences within the BLA. Thus, the findings provide additional evidence consistent with the hypothesis that the BLA has a general role in modulating memory consolidation.

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

“…the concentrations used in this study, which correspond to sub-threshold levels for receptor activation via a mono-target mechanism, are only able to evoke physiological effects by synergistic activation of several neurotransmitter systems (Youdim and Buccafusco, 2005;Cavalli et al, 2008). The memory-enhancing effects of dimebon may indicate simultaneous activity toward AMPA, NMDA, dopamine and serotonin receptors, all of which have been involved in inhibitory and appetitive hippocampus-dependent learning (Ungerer et al, 1998;Orsetti et al, 2001;Rogawski and Wenk, 2003;LaLumiere et al, 2003;Lynch and Gall, 2006;Balschun et al, 2006;Da Silva Costa et al, 2009;Benchenane et al, 2010). In particular, it has been hypothesised that dimebon's activity as a positive modulator of AMPA receptors and low affinity non-competitive blocker of NMDA receptors via a multi-drug mechanism, can explain the pro-cognitive action of this compound (Grigorev et al, 2003;Grigoriev 2009).…”

Mechanisms of fear extinction

“…Norepinephrine has been implicated as well in fear memory consolidation in more traditional Pavlovian fear conditioning paradigms 265,266 although there is some dispute as to the precise nature of its role. 267 Adrenergic involvement in extinction has been the topic of two recent studies, both of which employed Pavlovian fear conditioning in mice with freezing as a measure of conditioned fear.…”

Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear

“…All drugs were freshly prepared before the experiments. The doses of the drugs (10 mg/ml propranolol, 100 mg/ml anisomycin, 25 mg/ml emetine, 1.0 mg/ml Rp-cAMPs, and 0.3 or 1.0 mg/ml NE) were based on previous studies (LaLumiere et al, 2003;Lima et al, 2009;Moncada et al, 2011). The infusion volume of NE was 1.0 ml, and the infusion volume of the other drugs was 0.5 ml to minimize the total infusion volume (Katche et al, 2010).…”