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Article

Hippocampal 2-Arachidonoyl Glycerol Signaling Regulates Time-of-Day- and Stress-Dependent Effects on Rat Short-Term Memory

1
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy
2
Neurobiology of Behavior Laboratory, Santa Lucia Foundation, 00143 Rome, Italy
3
Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
4
Department of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, AB T2N 4N1, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(19), 7316; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197316
Received: 2 September 2020 / Revised: 25 September 2020 / Accepted: 1 October 2020 / Published: 3 October 2020
Background: Cannabinoids induce biphasic effects on memory depending on stress levels. We previously demonstrated that different stress intensities, experienced soon after encoding, impaired rat short-term recognition memory in a time-of-day-dependent manner, and that boosting endocannabinoid anandamide (AEA) levels restored memory performance. Here, we examined if two different stress intensities and time-of-day alter hippocampal endocannabinoid tone, and whether these changes modulate short-term memory. Methods: Male Sprague-Dawley rats were subjected to an object recognition task and exposed, at two different times of the day (i.e., morning or afternoon), to low or high stress conditions, immediately after encoding. Memory retention was assessed 1 hr later. Hippocampal AEA and 2-arachidonoyl glycerol (2-AG) content and the activity of their primary degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), were measured soon after testing. Results: Consistent with our previous findings, low stress impaired 1-hr memory performance only in the morning, whereas exposure to high stress impaired memory independently of testing time. Stress exposure decreased AEA levels independently of memory alterations. Interestingly, exposure to high stress decreased 2-AG content and, accordingly, increased MAGL activity, selectively in the afternoon. Thus, to further evaluate 2-AG’s role in the modulation of short-term recognition memory, rats were given bilateral intra-hippocampal injections of the 2-AG hydrolysis inhibitor KML29 immediately after training, then subjected to low or high stress conditions and tested 1 hr later. Conclusions: KML29 abolished the time-of-day-dependent impairing effects of stress on short-term memory, ameliorating short-term recognition memory performance. View Full-Text
Keywords: time-of-day; short-term memory; endocannabinoids; hippocampus; swim stress time-of-day; short-term memory; endocannabinoids; hippocampus; swim stress
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MDPI and ACS Style

Santori, A.; Morena, M.; Hill, M.N.; Campolongo, P. Hippocampal 2-Arachidonoyl Glycerol Signaling Regulates Time-of-Day- and Stress-Dependent Effects on Rat Short-Term Memory. Int. J. Mol. Sci. 2020, 21, 7316. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197316

AMA Style

Santori A, Morena M, Hill MN, Campolongo P. Hippocampal 2-Arachidonoyl Glycerol Signaling Regulates Time-of-Day- and Stress-Dependent Effects on Rat Short-Term Memory. International Journal of Molecular Sciences. 2020; 21(19):7316. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197316

Chicago/Turabian Style

Santori, Alessia, Maria Morena, Matthew N. Hill, and Patrizia Campolongo. 2020. "Hippocampal 2-Arachidonoyl Glycerol Signaling Regulates Time-of-Day- and Stress-Dependent Effects on Rat Short-Term Memory" International Journal of Molecular Sciences 21, no. 19: 7316. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197316

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