title: Novelty-induced emotional arousal modulates cannabinoid effects on recognition memory and adrenocortical activity.
abstract: 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.
authors: Department of Physiology and Pharmacology, Sapienza University of Rome, P.le A. Moro 5, Rome, Italy. patrizia.campolongo@uniroma1.it
authors: Patrizia
authors: P
authors: Campolongo
authors: Maria
authors: M
authors: Morena
authors: Sergio
authors: S
authors: Scaccianoce
authors: Viviana
authors: V
authors: Trezza
authors: Flavia
authors: F
authors: Chiarotti
authors: Gustav
authors: G
authors: Schelling
authors: Vincenzo
authors: V
authors: Cuomo
authors: Benno
authors: B
authors: Roozendaal
mesh_terms: D000818:Animals; D001143:Arousal; D048588:Benzoxazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004644:Emotions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009025:Morpholines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009281:Naphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects*; D012153:Retention, Psychology / Q000187:drug effects; D013997:Time Factors
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D004791:Enzyme Inhibitors; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003345:Corticosterone; D008797:Metyrapone