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Anandamide and 2-arachidonoylglycerol: Pharmacological Properties, Functional Features, and Emerging Specificities of the Two Major Endocannabinoids

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Abstract

Since the discovery of endocannabinoids and their receptors, two major members of the endocannabinoid family, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), have been regarded almost as twin brothers. Pharmacological properties were initially considered to be similar, as these molecules were believed mutually exchangeable and almost indistinguishable in the regulation of synaptic functions, such as long- and short-term synaptic plasticity, and in behavioral aspects, such as learning and memory, reward and addiction, antinociception, and anxiety. In recent years, however, endocannabinoid signaling specificity began to emerge, in particular, due to the production of genetically engineered mice lacking key enzymes in endocannabinoid synthesis or degradation, together with the development of selective inhibitors of AEA or 2-AG catabolic enzymes. Evidence now suggests that AEA and 2-AG possess specific pharmacological properties, are engaged in different forms of synaptic plasticity, and take part in different behavioral functions. In this review, we provide an overview on similarities and specificities of the two endocannabinoids in the CNS and on the unresolved questions concerning their role in synaptic signaling.

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Acknowledgments

This work was sponsored by a grant from the Italian Ministry of University to Marco Pistis (PRIN 2009: 200928EEX4). We wish to thank the Regione Autonoma della Sardegna, Assessorato alla Programmazione for the support given to Antonio Luchicchi (Bursaries for Young Researchers, Legge Regionale 7/2007).

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy

    Antonio Luchicchi & Marco Pistis

  2. CNR Neuroscience Institute, Cagliari, Italy

    Marco Pistis

  3. Center of Excellence for the Neurobiology of Addiction, University of Cagliari, Cagliari, Italy

    Marco Pistis

  4. Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042, Monserrato, Cagliari, Italy

    Marco Pistis

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  1. Antonio Luchicchi
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  2. Marco Pistis
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Correspondence to Marco Pistis.

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Luchicchi, A., Pistis, M. Anandamide and 2-arachidonoylglycerol: Pharmacological Properties, Functional Features, and Emerging Specificities of the Two Major Endocannabinoids. Mol Neurobiol 46, 374–392 (2012). https://doi.org/10.1007/s12035-012-8299-0

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  • DOI: https://doi.org/10.1007/s12035-012-8299-0

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