Anxiolytic-Like Properties of the Anandamide Transport Inhibitor AM404 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-12

AUTHORS

Marco Bortolato, Patrizia Campolongo, Regina Anne Mangieri, Maria Luisa Scattoni, Roberto Frau, Viviana Trezza, Giovanna La Rana, Roberto Russo, Antonio Calignano, Gian Luigi Gessa, Vincenzo Cuomo, Daniele Piomelli

ABSTRACT

The endocannabinoids anandamide and 2-arachidonoyglycerol (2-AG) may contribute to the regulation of mood and emotion. In this study, we investigated the impact of the endocannabinoid transport inhibitor AM404 on three rat models of anxiety: elevated plus maze, defensive withdrawal and separation-induced ultrasonic vocalizations. AM404 (1-5 mg kg(-1), intraperitoneal (i.p.)) exerted dose-dependent anxiolytic-like effects in the three models. These behavioral effects were associated with increased levels of anandamide, but not 2-AG, in the prefrontal cortex and were prevented by the CB(1) cannabinoid antagonist rimonabant (SR141716A), suggesting that they were dependent on anandamide-mediated activation of CB(1) cannabinoid receptors. We also evaluated whether AM404 might influence motivation (in the conditioned place preference (CPP) test), sensory reactivity (acoustic startle reflex) and sensorimotor gating (prepulse inhibition (PPI) of the startle reflex). In the CPP test, AM404 (1.25-10 mg kg(-1), i.p.) elicited rewarding effects in rats housed under enriched conditions, but not in rats kept in standard cages. Moreover, AM404 did not alter reactivity to sensory stimuli or cause overt perceptual distortion, as suggested by its lack of effect on startle or PPI of startle. These results support a role of anandamide in the regulation of emotion and point to the anandamide transport system as a potential target for anxiolytic drugs. More... »

PAGES

1301061

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.npp.1301061

DOI

http://dx.doi.org/10.1038/sj.npp.1301061

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015034477

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16541083


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435 https://www.grid.ac/institutes/grid.4691.a schema:alternateName University of Naples Federico II
436 schema:name Department of Experimental Pharmacology, University of Naples, Naples, Italy
437 rdf:type schema:Organization
438 https://www.grid.ac/institutes/grid.7763.5 schema:alternateName University of Cagliari
439 schema:name Department of Neuroscience ‘Bernard B. Brodie’, University of Cagliari, Cagliari, Italy
440 rdf:type schema:Organization
441 https://www.grid.ac/institutes/grid.7841.a schema:alternateName Sapienza University of Rome
442 schema:name Department of Human Physiology and Pharmacology, University of Rome ‘La Sapienza’, Rome, Italy
443 rdf:type schema:Organization
 




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