Brain and behavior · 2019
Lipidomic changes in the rat hippocampus following cocaine conditioning, extinction, and reinstatement of drug-seeking.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Pati Sumitra, Angel Peggi, Drake Richard R, Wagner John J, Cummings Brian S
Аннотация
INTRODUCTION: Cocaine dependence affects millions of individuals worldwide; however, there are no pharmacotherapeutic and/or diagnostic solutions. Recent evidence suggests a role for lipid signaling in the development and maintenance of addiction, highlighting the need to understand how lipid remodeling mediates neuroadaptation after cocaine exposure.
METHODS: This study utilized shotgun lipidomics to assess cocaine-induced lipid remodeling in rats using a novel behavioral regimen that incorporated multiple sessions of extinction training and reinstatement testing.
RESULTS: Mass spectrometric imaging demonstrated widespread decreases in phospholipid (PL) abundance throughout the brain, and high-spatial resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry indicated hippocampus-specific PL alterations following cocaine exposure. We analyzed the expression of genes involved in hippocampal lipid metabolism and observed region-specific regulation. In addition, we found that cocaine exposure differentially regulates mitochondrial biogenesis in the brain.
CONCLUSIONS: This work presents a comprehensive lipidomic assessment of cocaine-induced lipid remodeling in the rat brain. Further, these findings indicate a potential interplay between CNS energetics and differential lipid regulation and suggest a role for cocaine in the maintenance of energy homeostasis.
METHODS: This study utilized shotgun lipidomics to assess cocaine-induced lipid remodeling in rats using a novel behavioral regimen that incorporated multiple sessions of extinction training and reinstatement testing.
RESULTS: Mass spectrometric imaging demonstrated widespread decreases in phospholipid (PL) abundance throughout the brain, and high-spatial resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry indicated hippocampus-specific PL alterations following cocaine exposure. We analyzed the expression of genes involved in hippocampal lipid metabolism and observed region-specific regulation. In addition, we found that cocaine exposure differentially regulates mitochondrial biogenesis in the brain.
CONCLUSIONS: This work presents a comprehensive lipidomic assessment of cocaine-induced lipid remodeling in the rat brain. Further, these findings indicate a potential interplay between CNS energetics and differential lipid regulation and suggest a role for cocaine in the maintenance of energy homeostasis.