Basolateral amygdala noradrenergic activity mediates corticosterone-induced enhancement of auditory fear conditioning
Introduction
Glucocorticoids, released from the adrenal cortex during stressful situations, are known to facilitate the consolidation of long-term memories (de Kloet et al., 1999, McGaugh and Roozendaal, 2002, Roozendaal, 2000). Although most studies have investigated the memory-modulatory effects of glucocorticoids or specific glucocorticoid receptor (GR) agonists in emotionally arousing learning tasks that have a strong spatial and/or contextual component (Conrad et al., 1999, Cordero and Sandi, 1998, Micheau et al., 1985, Oitzl and de Kloet, 1992, Roozendaal and McGaugh, 1997b), recent findings indicate that they also enhance memory consolidation of other types of emotionally arousing learning experiences, including object recognition in a novel environment (Okuda, Roozendaal, & McGaugh, 2004). In contrast, glucocorticoid administration appears not to influence memory consolidation for less arousing or neutral information (Buchanan and Lovallo, 2001, Okuda et al., 2004). Extensive evidence indicates that glucocorticoids require a co-activation of noradrenergic mechanisms within the basolateral complex of the amygdala (BLA, consisting of the lateral, basal, and accessory basal nuclei) in modulating memory consolidation (Quirarte et al., 1997, Roozendaal, Nguyen, et al., 1999, Roozendaal et al., 2002). As emotionally arousing stimulation induces long-lasting activation of the BLA (Pelletier, Likhtik, Filali, & Paré, 2005), involving the release of norepinephrine (McIntyre, Hatfield, & McGaugh, 2002), we previously suggested that such a dependence of glucocorticoids on training-induced noradrenergic activity may underlie the selective involvement of glucocorticoids in modulating the consolidation of emotionally arousing information (Roozendaal, Okuda, de Quervain, & McGaugh, 2006).
The present experiment investigated whether posttraining noradrenergic activity in the BLA is required for mediating the enhancing effects of glucocorticoid administration on memory for auditory-cue classical fear conditioning. In classical or Pavlovian fear conditioning, an emotionally neutral stimulus, such as a tone, acquires the capacity to elicit defensive responses after association with a noxious stimulus, such as a footshock. Some findings have suggested that auditory-cue fear conditioning may differ from other emotionally arousing tasks in that memory for tone–shock pairing may be formed instantly in the lateral subdivision of the BLA (LeDoux, 2000). As a consequence, although pretraining manipulations of BLA activity may either enhance or impair fear learning, memory of auditory-cue fear conditioning should not be susceptible to posttraining systemic or intra-BLA drug manipulations (Debiec and LeDoux, 2004, Wilensky et al., 1999, Wilensky et al., 2000). However, recent findings indicate that posttraining administration of glucocorticoids also enhances memory consolidation of auditory-cue fear conditioning (Hui et al., 2004, Zorawski and Killcross, 2002). Additionally, glucocorticoids enhance Pavlovian appetitive discrete-cue conditioning (Zorawski & Killcross, 2002). In the present study, immediately after pairing of a single-frequency auditory stimulus with footshock, rats received bilateral infusions of the selective β1-adrenoceptor antagonist atenolol into the BLA together with systemic injections of corticosterone. Suppression of motor activity to the auditory stimulus was examined 24 h later in a novel test chamber and used as the measure of memory of the fear conditioning. This measure was used because it enables assessment of rapid changes in behavior in response to the onset of the conditioned stimulus. Previously, in an experiment using this measure of conditioning we reported that corticosterone selectively facilitated conditioned responding after paired presentations of the auditory stimulus and footshock without enhancing the behavioral response of rats given unpaired presentations of tone and shock (Hui et al., 2004).
Section snippets
Subjects
Young adult male Sprague–Dawley rats (weighing 280–320 g at time of surgery) from Charles River Breeding Laboratories (Wilmington, MA) were individually housed in a temperature-controlled (22 °C) vivarium on a standard 12/12-h light/dark cycle (lights on at 07:00 h) and given food and water ad libitum. Training and testing were performed between 10:00 and 15:00 h, at the rat’s nadir of the diurnal rhythm for corticosterone. All experimental procedures were performed in compliance with NIH
Results
This experiment investigated whether glucocorticoid effects on memory consolidation for auditory-cue fear conditioning require concurrent noradrenergic activity in the BLA. As shown in Fig. 2, infusions of the β1-adrenoceptor antagonist atenolol administered into the BLA immediately after training blocked the facilitating effect of systemic corticosterone injections on conditioned suppression of motor activity. Two-way ANOVA for mean movement during the 10-s time period immediately preceding
Discussion
The main finding of the present study is that posttraining infusions of the β1-adrenoceptor antagonist atenolol into the BLA blocked the enhancing effect of systemically administered corticosterone on memory for auditory-cue fear conditioning. These findings are consistent with previous evidence indicating that a β-adrenoceptor antagonist administered into the BLA after training blocked the enhancing effects of systemically administered glucocorticoids on memory for other kinds of emotionally
Acknowledgment
Research was supported by the United States Public Health Service Grant DC-05592 (NMW/JLM) from the National Institutes of Health.
References (42)
- et al.
Enhanced memory for emotional material following stress-level cortisol treatment in humans
Psychoneuroendocrinology
(2001) - et al.
Support for a bimodal role for type II adrenal steroid receptors in spatial memory
Neurobiology of Learning and Memory
(1999) - et al.
A role for brain glucocorticoid receptors in contextual fear conditioning: dependence upon training intensity
Brain Research
(1998) - et al.
Neurotransmission in the rat amygdala related to fear and anxiety
Trends in Neurosciences
(1994) - et al.
Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala
Neuroscience
(2004) - et al.
Stress and cognition: are corticosteroids good or bad guys?
Trends in Neurosciences
(1999) - et al.
Memory facilitating and anti-amnesic effects of corticosteroids
Pharmacology, Biochemistry and Behavior
(1978) - et al.
Norepinephrine release in the amygdala in response to footshock stimulation
Neurobiology of Learning and Memory
(1996) - et al.
Conditioned taste aversion and the pituitary–adrenal system
Behavioral Biology
(1976) - et al.
Memory enhancement of classical fear conditioning by post-training injections of corticosterone in rats
Neurobiology of Learning and Memory
(2004)
Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala
Neuroscience
Post-training injections of catecholaminergic drugs do not modulate fear conditioning in rats and mice
Neuroscience Letters
Role of adrenal stress hormones in forming lasting memories in the brain
Current Opinion in Neurobiology
Effects of dexamethasone on fear conditioning in pigs
Behavioral Biology
Type II glucocorticoid receptor antagonists impair contextual but not auditory-cue fear conditioning in juvenile rats
Neurobiology of Learning and Memory
Glucocorticoids and the regulation of memory consolidation
Psychoneuroendocrinology
Amygdaloid nuclei lesions differentially affect glucocorticoid-induced memory enhancement in an inhibitory avoidance task
Neurobiology of Learning and Memory
Glucocorticoid receptor agonist and antagonist administration into the basolateral but not central amygdala modulates memory storage
Neurobiology of Learning and Memory
Glucocorticoids interact with emotion-induced noradrenergic activation in influencing different memory functions
Neuroscience
Regulation of α and β components of noradrenergic cyclic cAMP response in cortical slices
European Journal of Pharmacology
Posttraining glucocorticoid receptor agonist enhances memory in appetitive and aversive Pavlovian discrete-cue conditioning paradigms
Neurobiology of Learning and Memory
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