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.
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Acknowledgements
We thank Daniela Valeri and Veronica Carrara for technical help. This study was supported by grants from Sapienza University ‘Progetti di Ricerca di Università’, Vigoni Project (Ateneo Italo Tedesco) to PC and GS and from MIUR, FIRB Futuro in Ricerca to PC.
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Campolongo, P., Morena, M., Scaccianoce, S. et al. Novelty-Induced Emotional Arousal Modulates Cannabinoid Effects on Recognition Memory and Adrenocortical Activity. Neuropsychopharmacol 38, 1276–1286 (2013). https://doi.org/10.1038/npp.2013.26
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DOI: https://doi.org/10.1038/npp.2013.26
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