Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation

Patrizia Ratano, Carla Petrella, Fabrizio Forti, Pamela Petrocchi Passeri, Maria Morena, Maura Palmery, Viviana Trezza, Cinzia Severini, Patrizia Campolongo

Research output: Contribution to journalArticle

Abstract

The endocannabinoid system is a key modulator of memory consolidation for aversive experiences. We recently found that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases anandamide levels by inhibiting its hydrolysis, facilitates memory consolidation through a concurrent activation of both cannabinoid receptor type 1 (CB1) and 2 (CB2). Here, we investigated the role played on memory consolidation by the other major endocannabinoid, 2-arachidonoylglycerol (2-AG). To this aim, we tested the effects of pharmacological inhibition of monoacylglycerol lipase (MAGL) through systemic administration of the MAGL inhibitor JZL184 to rats immediately after training of the inhibitory avoidance task. Pharmacological enhancement of 2-AG tone facilitated memory consolidation through activation of CB2 receptor signaling. Moreover, we found that increased 2-AG signaling prevented the activation of the mammalian target of rapamycin (mTOR) signaling pathway in the hippocampus through a CB2-dependent mechanism. Our results identify a fundamental role for 2-AG and CB2 receptors in the modulation of memory consolidation for aversive experiences.

Original languageEnglish
Pages (from-to)210-218
Number of pages9
JournalNeuropharmacology
Volume138
DOIs
Publication statusPublished - Aug 2018

Fingerprint

Cannabinoid Receptor CB1
Sirolimus
Hydrolysis
Pharmacology
Monoacylglycerol Lipases
Endocannabinoids
Hippocampus
Memory Consolidation
Inhibition (Psychology)
2-arachidonylglycerol

Cite this

Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation. / Ratano, Patrizia; Petrella, Carla; Forti, Fabrizio; Passeri, Pamela Petrocchi; Morena, Maria; Palmery, Maura; Trezza, Viviana; Severini, Cinzia; Campolongo, Patrizia.

In: Neuropharmacology, Vol. 138, 08.2018, p. 210-218.

Research output: Contribution to journalArticle

Ratano, Patrizia ; Petrella, Carla ; Forti, Fabrizio ; Passeri, Pamela Petrocchi ; Morena, Maria ; Palmery, Maura ; Trezza, Viviana ; Severini, Cinzia ; Campolongo, Patrizia. / Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation. In: Neuropharmacology. 2018 ; Vol. 138. pp. 210-218.
@article{12ecc34d84284ecaa04a9dcf34509925,
title = "Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation",
abstract = "The endocannabinoid system is a key modulator of memory consolidation for aversive experiences. We recently found that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases anandamide levels by inhibiting its hydrolysis, facilitates memory consolidation through a concurrent activation of both cannabinoid receptor type 1 (CB1) and 2 (CB2). Here, we investigated the role played on memory consolidation by the other major endocannabinoid, 2-arachidonoylglycerol (2-AG). To this aim, we tested the effects of pharmacological inhibition of monoacylglycerol lipase (MAGL) through systemic administration of the MAGL inhibitor JZL184 to rats immediately after training of the inhibitory avoidance task. Pharmacological enhancement of 2-AG tone facilitated memory consolidation through activation of CB2 receptor signaling. Moreover, we found that increased 2-AG signaling prevented the activation of the mammalian target of rapamycin (mTOR) signaling pathway in the hippocampus through a CB2-dependent mechanism. Our results identify a fundamental role for 2-AG and CB2 receptors in the modulation of memory consolidation for aversive experiences.",
author = "Patrizia Ratano and Carla Petrella and Fabrizio Forti and Passeri, {Pamela Petrocchi} and Maria Morena and Maura Palmery and Viviana Trezza and Cinzia Severini and Patrizia Campolongo",
note = "Copyright {\circledC} 2018 Elsevier Ltd. All rights reserved.",
year = "2018",
month = "8",
doi = "10.1016/j.neuropharm.2018.05.030",
language = "English",
volume = "138",
pages = "210--218",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Pharmacological inhibition of 2-arachidonoilglycerol hydrolysis enhances memory consolidation in rats through CB2 receptor activation and mTOR signaling modulation

AU - Ratano, Patrizia

AU - Petrella, Carla

AU - Forti, Fabrizio

AU - Passeri, Pamela Petrocchi

AU - Morena, Maria

AU - Palmery, Maura

AU - Trezza, Viviana

AU - Severini, Cinzia

AU - Campolongo, Patrizia

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018/8

Y1 - 2018/8

N2 - The endocannabinoid system is a key modulator of memory consolidation for aversive experiences. We recently found that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases anandamide levels by inhibiting its hydrolysis, facilitates memory consolidation through a concurrent activation of both cannabinoid receptor type 1 (CB1) and 2 (CB2). Here, we investigated the role played on memory consolidation by the other major endocannabinoid, 2-arachidonoylglycerol (2-AG). To this aim, we tested the effects of pharmacological inhibition of monoacylglycerol lipase (MAGL) through systemic administration of the MAGL inhibitor JZL184 to rats immediately after training of the inhibitory avoidance task. Pharmacological enhancement of 2-AG tone facilitated memory consolidation through activation of CB2 receptor signaling. Moreover, we found that increased 2-AG signaling prevented the activation of the mammalian target of rapamycin (mTOR) signaling pathway in the hippocampus through a CB2-dependent mechanism. Our results identify a fundamental role for 2-AG and CB2 receptors in the modulation of memory consolidation for aversive experiences.

AB - The endocannabinoid system is a key modulator of memory consolidation for aversive experiences. We recently found that the fatty acid amide hydrolase (FAAH) inhibitor URB597, which increases anandamide levels by inhibiting its hydrolysis, facilitates memory consolidation through a concurrent activation of both cannabinoid receptor type 1 (CB1) and 2 (CB2). Here, we investigated the role played on memory consolidation by the other major endocannabinoid, 2-arachidonoylglycerol (2-AG). To this aim, we tested the effects of pharmacological inhibition of monoacylglycerol lipase (MAGL) through systemic administration of the MAGL inhibitor JZL184 to rats immediately after training of the inhibitory avoidance task. Pharmacological enhancement of 2-AG tone facilitated memory consolidation through activation of CB2 receptor signaling. Moreover, we found that increased 2-AG signaling prevented the activation of the mammalian target of rapamycin (mTOR) signaling pathway in the hippocampus through a CB2-dependent mechanism. Our results identify a fundamental role for 2-AG and CB2 receptors in the modulation of memory consolidation for aversive experiences.

U2 - 10.1016/j.neuropharm.2018.05.030

DO - 10.1016/j.neuropharm.2018.05.030

M3 - Article

C2 - 29842858

VL - 138

SP - 210

EP - 218

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -