Title

 

Authors

M. Morena¹, V. Trezza², P. Ratano¹, C. Pecci¹, M. Palmery¹, P. Campolongo¹, V. Cuomo¹

1 Dept. of Physiology and Pharmacology, Sapienza University of Rome, Italy
2 Dept. of Biology, University of Roma Tre, Rome, Italy
 

 

Abstract

Emotions have a powerful impact on memory. Numerous studies have shown that the most vivid memories tend to be of emotional events. Extensive evidence indicates that the basolateral complex of the amygdala (BLA), medial prefrontal cortex (mPFC) and hippocampus (Hipp) modulate memories for emotionally arousing experiences (Roozendaal 2003). We have recently shown that bilateral intra-BLA infusion of the cannabinoid receptor agonist WIN55,212-2 immediately after inhibitory avoidance training enhanced memory consolidation in rats (Campolongo et al., 2009). However, the use of drugs that directly bind and activate brain cannabinoid receptors may be limited by their abuse liability. Nowadays, indirect cannabinoid agonists, that increase endocannabinoid signalling by interfering with endocannabinoid degradation, are emerging as a novel therapeutic approach for the treatment of central nervous system disorders. To study the effects of the FAAH inhibitor URB597 in the modulation of memory consolidation we tested male adult Sprague-Dawley rats (280-320 g at the time of surgery) on an inhibitory avoidance task. URB597 or its vehicle (5% PEG, 5% TWEEN, 90% saline) were infused into the BLA, into the mPFC or into the Hipp (3, 10, 30 ng per side). In another set of experiments, a non impairing dose of the CB1 receptor antagonist, AM251, (or its vehicle: 5% PEG, 5% TWEEN, 90% saline) was concurrently administered with URB597. All drugs were infused immediately after training. Only animals with needle tips located within the boundaries of the brain target areas and no damage to the target tissues were included in the final analysis. Immediately posttraining infusions of URB597 into all the three target areas induced enhancement of 48h inhibitory avoidance retention performance. Concurrent infusions of a low and non-impairing dose of AM251 blocked the memory enhancement induced by the administration of URB597, indicating that the memory-enhancing effects of URB597 are mediated by a selective activation of CB1 receptors. Our findings provide evidence that the endocannabinoid system in the limbic system is involved in modulating the consolidation of aversive memories.

Campolongo et al. (2009) Proc Natl Acad Sci U S A. 106, 4888–4893.
Roozendaal (2003) Prog Neuropsychopharmacol Biol Psychiatry. 27, 1213-1223.