期刊
CURRENT PHARMACEUTICAL DESIGN
卷 19, 期 40, 页码 7036-7049出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161281940131209143421
关键词
Oleoylethanolamide; PPAR alpha; knockout; cocaine; motor sensitization; reinforcement
资金
- Red de Trastornos Adictivos RETICS network from the Spanish Health Institute Carlos III [RD06/0001/0000, RD012/0028/0001]
- Andalusian Health Service [SAS 111224]
- Fundacio La Telemarato [TV3 386/C/2011]
- Andalusian Ministry of Economy, Innovation and Science [EU-ERDF CTS-433]
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.
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