Abstract
Cocaine dependence displays a broad impairment in cognitive performance including attention, learning, and memory. To obtain a better understanding of the action of cocaine in the nervous system, and the relation between phospholipids and memory, we have investigated whether phospholipids recover in the brain following cocaine removal using the fly model, Drosophila melanogaster. In addition, the effects of methylphenidate, a substitute medication for cocaine dependence, on fly brain lipids after cocaine abuse are also determined to see if it can rescue the lipid changes caused by cocaine. Time of flight secondary ion mass spectrometry with a (CO2)6000+ gas cluster ion beam was used to detect intact phospholipids. We show that cocaine has persistent effects, both increasing and decreasing the levels of specific phosphatidylethanolamines and phosphatidylinositols. These changes remain after cocaine withdrawal and are not rescued by methylphenidate. Cocaine is again shown to generally increase the levels of phosphatidylcholines in the fly brain; however, after drug withdrawal, the abundance of these lipids returns to the original level and methylphenidate treatment of the flies following cocaine exposure enhances the reversal of the lipid level reducing them below the original control. The study provides insight into the molecular effects of cocaine and methylphenidate on brain lipids. We suggest that phosphatidylcholines could be a potential target for the treatment of cocaine abuse as well as be a significant hallmark of cognition and memory loss with cocaine.
Highlights
Cocaine addiction is a worldwide serious health problem
One of the primary mechanisms of cocaine action is its ability to block presynaptic dopamine transporters which results in an increase in dopamine levels in the synaptic cleft resulting in euphoria and reinforcement of the administration of cocaine
Various neurological disorders and brain diseases such as Alzheimer’s, ischemic stroke, attention deficit hyperactivity disorder (ADHD), and schizophrenia have been shown to result in alteration of brain lipids regarding their localization, abundance, and metabolism.[8−12] MPH, as a common drug for ADHD patients, has been shown to change the lipid structure of the Drosophila melanogaster brain, especially by decreasing the abundance of cylindrical shaped PCs, and increasing the amount of conical shaped phosphatidylethanolamine (PEs) and phosphatidylinositols (PIs).[13]
Summary
Cocaine addiction is a worldwide serious health problem. One of the primary mechanisms of cocaine action is its ability to block presynaptic dopamine transporters which results in an increase in dopamine levels in the synaptic cleft resulting in euphoria and reinforcement of the administration of cocaine. Tors for neuronal signaling and transmission, and supply energy for brain activity.[5] Phospholipids are composed of different groups with specific types of headgroups and tails, which determines their physical and chemical properties as well as their shapes and morphologies These properties in turn result in different effects of the lipids on the activities of other neuronal molecules, for example, alteration of presynaptic protein interactions, activity of ion channels, and membrane curvature and fluidity.[6] Phosphatidylcholines (PCs) and cholesterol have been shown to diminish in the cellular membrane of PC12 cells following exposure to cisplatin, and this is suggested as a molecular mechanism underlying the change of neurotransmitter release by this drug.[7] In addition, various neurological disorders and brain diseases such as Alzheimer’s, ischemic stroke, ADHD, and schizophrenia have been shown to result in alteration of brain lipids regarding their localization, abundance, and metabolism.[8−12] MPH, as a common drug for ADHD patients, has been shown to change the lipid structure of the Drosophila melanogaster brain, especially by decreasing the abundance of cylindrical shaped PCs, and increasing the amount of conical shaped phosphatidylethanolamine (PEs) and phosphatidylinositols (PIs).[13] from our previous study comparing the effects of cocaine and MPH on the lipid structure of the fly brain,[14] it is apparent that these two drugs lead to opposite changes in differing phospholipid levels. These seem to be more permanent changes that cannot be rescued
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