Novelty-induced emotional arousal modulates cannabinoid effects on recognition memory and adrenocortical activity

Neuropsychopharmacology. 2013 Jun;38(7):1276-86. doi: 10.1038/npp.2013.26. Epub 2013 Jan 22.


Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3, or 1.0 mg/kg) on short- and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial, biphasically impaired retention performance at a 1-h interval. In contrast, WIN55,212-2 enhanced 1-h retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-h retention, enhanced object recognition performance at a 24-h interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-h retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1- and 24-h retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short- and long-term retention of object recognition memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arousal*
  • Benzoxazines / antagonists & inhibitors
  • Benzoxazines / pharmacology*
  • Cannabinoid Receptor Agonists / pharmacology
  • Corticosterone / blood*
  • Dose-Response Relationship, Drug
  • Emotions*
  • Enzyme Inhibitors / pharmacology
  • Exploratory Behavior / drug effects*
  • Habituation, Psychophysiologic / drug effects*
  • Hypothalamo-Hypophyseal System / drug effects
  • Male
  • Metyrapone / pharmacology
  • Morpholines / antagonists & inhibitors
  • Morpholines / pharmacology*
  • Naphthalenes / antagonists & inhibitors
  • Naphthalenes / pharmacology*
  • Pituitary-Adrenal System / drug effects
  • Rats
  • Recognition, Psychology / drug effects*
  • Retention, Psychology / drug effects
  • Time Factors


  • Benzoxazines
  • Cannabinoid Receptor Agonists
  • Enzyme Inhibitors
  • Morpholines
  • Naphthalenes
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Corticosterone
  • Metyrapone