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

Abstract

Background Lipid profiles in the blood are altered in human cocaine users, suggesting that cocaine-exposure can induce lipid remodeling. Methods Cocaine-induced locomotor sensitization in rats was followed by shotgun lipidomics using electrospray ionization-mass spectrometry (ESI-MS) and determined changes in brain tissues. To determine if any lipidomic changes were also reflected in the blood, we performed principal component analysis (PCA) of lipidomic spectra isolated from cocaine-treated animals. Alterations in the abundance of phospholipid species were correlated with behavioral changes in the magnitude of either the initial response to 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. 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 (R2 of 0.7 or higher) with either the initial response to cocaine or locomotor sensitization. Conclusion Taken together, these data demonstrate that a cocaine-conditioning experience results in the remodeling of specific phospholipids in rat brain tissue in a region-specific manner and also alters the intensities and 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.

Cyclin-Dependent Kinase Inhibitor 1a (p21) Modulates Response to Cocaine and Motivated Behaviors

“…The behavioral results for the initial rat locomotor sensitization (LMS) experiment have been published as part of another recent study, and these animals exhibited the expected increase in locomotor activity on the challenge day relative to the activity day (Cummings et al, 2015). For the assessment of LMS, the animal was placed in the center of an open field chamber for 30 minutes to determine baseline movement during the activity day (day 2).…”

Lipidomic changes in the rat hippocampus following cocaine conditioning, extinction, and reinstatement of drug‐seeking

“…Additionally, pathways which stimulate the release of arachidonic acid, such as activators of phospholipase A 2 , were shown to exhibit inhibitory effects on dopamine uptake, while dietary deficiency in α‐linolenic acid, the precursor of long‐chain n‐3 polyunsaturated fatty acids (PUFA), altered dopaminergic neurotransmission (Zhang & Reith, ; Zimmer et al, ). Lipid remodeling following cocaine exposure has also been linked with behaviors such as drug relapse and behavioral sensitization (Buydens‐Branchey et al, ; Cummings et al, ). Our prior work was the first to report that cocaine induces region‐specific changes in select lipid species in the rat brain and the blood using a preclinical model of drug exposure resulting in behavioral sensitization (Cummings et al, ).…”

“…Lipid remodeling following cocaine exposure has also been linked with behaviors such as drug relapse and behavioral sensitization (Buydens‐Branchey et al, ; Cummings et al, ). Our prior work was the first to report that cocaine induces region‐specific changes in select lipid species in the rat brain and the blood using a preclinical model of drug exposure resulting in behavioral sensitization (Cummings et al, ).…”

Psychostimulants, Brain Membrane Lipids and Dopamine Transmission

“…For example, repeated, intermittent injections of cocaine (10-15 mg/kg, i.p.) to male Sprague Dawley rats induce locomotor sensitization, which paralleled changes in brain phospholipids one week after the last cocaine injection [2]. Specifically, cocaine exposure increased phospholipid levels in the hippocampus and the ventral striatum.…”

“…Although the molecular mechanisms underlying psychostimulant-induced changes in transporters and receptors remain elusive, emerging evidence implicates brain lipids as potential mediators [2]. This review aims to provide a current understanding of the association between chronic psychostimulant exposure and brain membrane lipid profile and highlight the potential contribution of dysregulated brain membrane lipids to altered neurotransmission and associated addiction behavior.…”