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  • Mouro_et_al-2018-Journal_of_Neurochemistry

    Rights statement: This is the peer reviewed version of the following article: Mouro, F. M., Ribeiro, J. A., Sebastião, A. M. and Dawson, N. (2018), Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity. J. Neurochem., 147: 71-83. doi:10.1111/jnc.14549 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jnc.14549/abstract This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

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Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity

Research output: Contribution to journalJournal articlepeer-review

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  • Francisco M Mouro
  • Joaquim A Ribeiro
  • Ana M Sebastião
  • Neil Dawson
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<mark>Journal publication date</mark>10/2018
<mark>Journal</mark>Journal of Neurochemistry
Issue number1
Volume147
Number of pages13
Pages (from-to)71-83
Publication StatusPublished
Early online date10/07/18
<mark>Original language</mark>English

Abstract

Elucidating how cannabinoids affect brain function is instrumental for the development of therapeutic tools aiming to mitigate 'on target' side effects of cannabinoid based therapies. A single treatment with the cannabinoid receptor agonist, WIN 55,212-2, disrupts recognition memory in mice. Here we evaluate how prolonged, intermittent (30 days) exposure to WIN 55,212-2 (1mg/kg) alters recognition memory and impacts on brain metabolism and functional connectivity. We show that chronic, intermittent treatment with WIN 55,212-2 disrupts recognition memory (Novel Object Recognition Test) without affecting locomotion and anxiety-like behaviour (Open Field and Elevated Plus Maze). Through 14 C-2-deoxyglucose functional brain imaging we show that chronic, intermittent WIN 55,212-2 exposure induces hypometabolism in the hippocampal dorsal subiculum and in the mediodorsal nucleus of the thalamus, two brain regions directly involved in recognition memory. In addition, WIN 55,212-2 exposure induces hypometabolism in the habenula with a contrasting hypermetabolism in the globus pallidus. Through the application of the Partial Least Squares Regression (PLSR) algorithm to the brain imaging data, we observed that prolonged WIN 55,212-2 administration alters functional connectivity in brain networks that underlie recognition memory, including that between the hippocampus and prefrontal cortex, the thalamus and prefrontal cortex, and between the hippocampus and the perirhinal cortex. In addition, our results support disturbed lateral habenula and serotonin system functional connectivity following WIN 55,212-2 exposure. Overall, this study provides new insight into the functional mechanisms underlying the impact of chronic cannabinoid exposure on memory and highlights the serotonin system as a particularly vulnerable target. This article is protected by copyright. All rights reserved.

Bibliographic note

This is the peer reviewed version of the following article: Mouro, F. M., Ribeiro, J. A., Sebastião, A. M. and Dawson, N. (2018), Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity. J. Neurochem., 147: 71-83. doi:10.1111/jnc.14549 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jnc.14549/abstract This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.