title: Lipid transmitter signaling as a new target for treatment of cocaine addiction: new roles for acylethanolamides and lysophosphatidic acid.
abstract: This review analyzes the roles of lipid transmitters, especially those derived from the cleavage of membrane phospholipids, in cocaine-associated behaviors. These lipid signals are important modulators of information processing in the brain, affecting transmitter release, neural plasticity, synaptogenesis, neurogenesis, and cellular energetics. This broad range of actions makes them suitable targets for pharmaceutical development of cocaine addiction therapies because they participate in the main cellular processes underlying the neuroadaptations associated with chronic use of this psychostimulant. The main lipid transmitters reviewed here include a) acylethanolamides and acylglycerols acting on cannabinoid receptors, such as anandamide and 2-arachidonoylglycerol; b) acylethanolamides that do not act on cannabinoid receptors, such as oleoylethanolamide; c) eicosanoids derived from arachidonic acid, including prostaglandins; and d) lysophosphatidic acid, focusing on the role of its LPA-1 receptor. Direct experimental evidence for the significance of these lipids in cocaine-related behaviors is presented and discussed. Additionally, the roles for both their biosynthesis and degradation pathways, as well as the participation of their receptors, are examined. Overall, lipid transmitter signaling can offer new targets for the development of therapies for cocaine addiction.
authors.affiliation: Hospital Carlos Haya de Málaga. Avda. Carlos Haya 82, E-29010 Málaga, Spain. fernando.rodriguez@fundacionimabis.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Orio
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Pavón
authors.forename: Eduardo
authors.initials: E
authors.lastname: Blanco
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.forename: Pedro
authors.initials: P
authors.lastname: Araos
authors.forename: María
authors.initials: M
authors.lastname: Pedraz
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.forename: Montserrat
authors.initials: M
authors.lastname: Calado
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
authors.forename: Fernando Rodríguez
authors.initials: FR
authors.lastname: de Fonseca
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000503:physiopathology*; D015195:Drug Design; D015777:Eicosanoids; D006801:Humans; D008055:Lipids / Q000502:physiology*; D008246:Lysophospholipids / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010743:Phospholipids / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015777:Eicosanoids; D008055:Lipids; D008246:Lysophospholipids; D010743:Phospholipids