Posttraining Glucocorticoid Receptor Agonist Enhances Memory in Appetitive and Aversive Pavlovian Discrete-Cue Conditioning Paradigms

doi:10.1006/nlme.2002.4075

Neurobiology of Learning and Memory

Volume 78, Issue 2, September 2002, Pages 458-464

https://doi.org/10.1006/nlme.2002.4075 Get rights and content

Abstract

Glucocorticoid modulation of emotional memory has repeatedly been shown in aversive learning paradigms, but has received little attention in appetitive tasks. It has also been suggested that it may be selective for contextual cues. In order to investigate if glucocorticoids can modulate memory in discrete-cue conditioning of both appetitive and aversive tasks, two experiments were carried out. Male Lister-Hooded rats received pairings of an auditory cue and either food-reward (experiment 1) or footshock (experiment 2), followed immediately by posttraining injections of the glucocorticoid receptor agonist dexamethasone (0.3, 0.6, and 1.2 mg/kg) or vehicle. Dexamethasone (1.2 mg/kg) led to significantly enhanced learning. These results give support to the notion that glucocorticoids play a role in the modulation of both appetitive and aversive emotional memories and show that their role in learning goes beyond the construction of context representations. The modulation of appetitive and aversive discrete-cue learning may be subserved by a common mechanism.

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Systemic administration of drugs that activate the noradrenergic or glucocorticoid system potentiates aversive memory consolidation and reconsolidation. The opposite happens with the stimulation of endocannabinoid signaling under certain conditions. An unbalance of these interacting neurotransmitters can lead to the formation and maintenance of traumatic memories, whose strength and specificity attributes are often maladaptive. Here we aimed to investigate whether originally low-intensity and precise contextual fear memories would turn similar to traumatic ones in rats systemically administered with adrenaline, corticosterone, and/or the cannabinoid type-1 receptor antagonist/inverse agonist AM251 during consolidation or reconsolidation. The high dose of each pharmacological agent evaluated significantly increased freezing times at test in the conditioning context one and nine days later when given alone post-acquisition or post-retrieval. Their respective low dose produced no relative changes when given separately, but co-treatment of adrenaline with corticosterone or AM251 and the three drugs combined, but not corticosterone with AM251, produced results equivalent to those mentioned initially. Neither the high nor the low dose of adrenaline, corticosterone, or AM251 altered freezing times at test in a novel, neutral context two and ten days later. In contrast, animals receiving the association of their low dose exhibited significantly higher freezing times than controls. Together, the results indicate that newly acquired and destabilized threat memory traces become more intense and generalized after a combined interference acting synergistically and mimicking that reported in patients presenting stress-related psychiatric conditions.
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^☆: The authors thank Dr. Etienne Coutureau, Dr. Pam Blundell, and Dr. Vincent Casteras for their support and helpful comments. The work was conducted as part of a Ph.D. thesis (M.Z.) and was supported by an MRC research grant to S.K.

^f2: Address correspondence and reprint requests to Simon Killcross. Fax: +44 29 20874858. E-mail: [email protected].

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Brief ReportPosttraining Glucocorticoid Receptor Agonist Enhances Memory in Appetitive and Aversive Pavlovian Discrete-Cue Conditioning Paradigms☆

Abstract

Psychoneuroendocrinology

Brain Research

Pharmacology, Biochemistry and Behavior

Brain Research

Behavioral and Neural Biology

Brain Research Reviews

Neurobiology of Learning and Memory

Psychoneuroendocrinology

Neurobiology of Learning and Memory

Neurobiology of Learning and Memory

Brain Research

Lesions of the basolateral amygdala disrupt selective aspects of reinforcer representation in rats

Journal of Neuroscience

Brief Report
Posttraining Glucocorticoid Receptor Agonist Enhances Memory in Appetitive and Aversive Pavlovian Discrete-Cue Conditioning Paradigms☆