Lipid Transmitter Signaling as a New Target for Treatment of Cocaine Addiction: New Roles for Acylethanolamides and Lysophosphatidic Acid
Francisco Javier Pavón,
Fernando Rodríguez de Fonseca.
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.
Keywords: Oleoylethanolamide, PPARα, knockout, cocaine, motor sensitization, reinforcement.
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