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

Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4888-93. doi: 10.1073/pnas.0900835106. Epub 2009 Mar 2.


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 microL 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 microL 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 microL 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 microL per side) blocked the memory-enhancing effect induced by systemic administration of corticosterone (3 mg/kg, s.c.). These findings indicate that endocannabinoids 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / cytology
  • Amygdala / drug effects
  • Amygdala / metabolism*
  • Animals
  • Avoidance Learning / drug effects
  • Benzoxazines / administration & dosage
  • Benzoxazines / pharmacology
  • Cannabinoid Receptor Modulators / metabolism*
  • Corticosterone / pharmacology*
  • Endocannabinoids*
  • Male
  • Memory / drug effects*
  • Memory / physiology*
  • Morpholines / administration & dosage
  • Morpholines / pharmacology
  • Naphthalenes / administration & dosage
  • Naphthalenes / pharmacology
  • Piperidines / administration & dosage
  • Piperidines / pharmacology
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors


  • Benzoxazines
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • AM 251
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Corticosterone