Differential effects of cocaine exposure on the abundance of phospholipid species in rat brain and blood.

BACKGROUND

Lipid profiles in the blood are altered in human cocaine users, suggesting that cocaine exposure can induce lipid remodeling.

METHODS

Lipid changes in the brain tissues of rats sensitized to cocaine were determined through shotgun lipidomics using electrospray ionization-mass spectrometry (ESI-MS). We also performed pairwise principal component analysis (PCA) to assess cocaine-induced changes in blood lipid profiles. Alterations in the abundance of phospholipid species were correlated with behavioral changes in the magnitude of either the initial response to the drug or locomotor sensitization.

RESULTS

Behavioral sensitization altered the relative abundance of several phospholipid species in the hippocampus and cerebellum, measured one week following the final exposure to cocaine. In contrast, relatively few effects on phospholipids in either the dorsal or the ventral striatum were observed. PCA analysis demonstrated that cocaine altered the relative abundance of several glycerophospholipid species as compared to saline-injected controls in blood. Subsequent MS/MS analysis identified some of these lipids as phosphatidylethanolamines, phosphatidylserines and phosphatidylcholines. The relative abundance of some of these phospholipid species were well-correlated (R(2) of 0.7 or higher) with either the initial response to cocaine or locomotor sensitization.

CONCLUSION

Taken together, these data demonstrate that a cocaine-induced sensitization assay results in the remodeling of specific phospholipids in rat brain tissue in a region-specific manner and also alters the intensities of certain types of phospholipid species in rat blood. These results further suggest that such changes may serve as biomarkers to assess the neuroadaptations occurring following repeated exposure to cocaine.