Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

Patrizia Campolongo*, Benno Roozendaal, Viviana Trezza, Daniela Hauer, Gustav Schelling, James L. McGaugh, Vincenzo Cuomo

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    217 Citations (Scopus)

    Abstract

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors, the present experiments investigated whether the endocannabinoid system in the BLA influences memory consolidation and whether glucocorticoids interact with this system. The CB1 receptor agonist WIN55,212-2 (5-50 ng per 0.2 mu L per side), infused bilaterally into the BLA of male Sprague-Dawley rats immediately after inhibitory avoidance training, induced dose-dependent enhancement of 48-h retention. Conversely, the CB1 receptor antagonist AM251 (0.07-0.28 ng per 0.2 mu L per side) administered after training into the BLA induced inhibitory avoidance retention impairment. Furthermore, intra-BLA infusions of a low and nonimpairing dose of AM251 (0.14 ng per 0.2 mu L per side) blocked the memory enhancement induced by concurrent administration of WIN55,212-2. Delayed infusions of WIN55,212-2 or AM251 administered into the BLA 3 h after training or immediate posttraining infusions of these drugs into the adjacent central amygdala did not significantly alter retention performance. Last, intra-BLA infusions of a low and otherwise nonimpairing dose of AM251 (0.14 ng per 0.2 mu L per side) blocked the memory-enhancing effect induced by systemic administration of corticosterone (3 mg/kg, s.c.). These findings indicate that endo-cannabinoids in the BLA enhance memory consolidation and suggest that CB1 activity within this brain region is required for enabling glucocorticoid effects on memory consolidation enhancement.

    Original languageEnglish
    Pages (from-to)4888-4893
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume106
    Issue number12
    DOIs
    Publication statusPublished - 24-Mar-2009

    Keywords

    • AM251
    • cannabinoid receptors
    • emotional arousal
    • inhibitory avoidance
    • WIN55,212-2
    • CB1 CANNABINOID RECEPTORS
    • PITUITARY-ADRENAL AXIS
    • LONG-TERM POTENTIATION
    • EMOTIONALLY AROUSING EXPERIENCES
    • ENDOGENOUS CANNABINOIDS
    • SELECTIVE ANTAGONIST
    • INHIBITORY AVOIDANCE
    • STRESS HORMONES
    • IN-VIVO
    • BRAIN

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