Journal Article

Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

Piray Atsak, Patrizia Ratano, James L. McGaugh, Luigia Trabace, Gustav Schelling, Daniela Hauer, Vincenzo Cuomo, Patrizia Campolongo, Benno Roozendaal, Viviana Trezza, Maria Morena, Andrea Peloso

2014

Overview

Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontal-limbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation. Significance An involvement of exogenous cannabinoids in the regulation of memory for emotional events has emerged over the past decade. The present findings demonstrate that after an aversive training experience the endogenous cannabinoid anandamide is released into the amygdala, hippocampus, and medial prefrontal cortex (mPFC) and normally plays a role in the formation of a strong memory trace. Furthermore, an intact basolateral amygdala is required to coordinate both hippocampal and mPFC endocannabinoid activity during aversive memory consolidation. Thus, our findings provide the first evidence, to our knowledge, that a dynamic network involving anandamide signaling within this prefrontal-limbic circuit modulates the consolidation of memory for emotionally arousing training.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Amidohydrolases - antagonists & inhibitors / amygdala / Animal memory / Animals / Arachidonic Acids - metabolism / Avoidance Learning / Benzamides - pharmacology / Biological Sciences / Brain / cannabinoids / Carbamates - pharmacology / Comparative analysis / cortex / Emotions / Endocannabinoids - metabolism / Fatty acids / Glycerides - metabolism / Glycerol / hippocampus / Limbic System - enzymology / Limbic System - physiology / Memory / Polyunsaturated Alkamides - metabolism / Prefrontal Cortex - enzymology / Prefrontal Cortex - physiology / Rats / Receptor, Cannabinoid, CB1 - agonists / Rodents / Training