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The role of sphingolipids in psychoactive drug use and addiction

  • High Impact Review in Neuroscience, Neurology or Psychiatry - Review Article
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Abstract

Psychoactive drug use is a common behavior in many societies worldwide, frequently associated with drug instrumentalization. Regular use may develop into drug addiction, which is a severe psychiatric disorder with multiple pathological effects to virtually all organ systems. Treatment strategies for addiction are often insufficient with no broadly working pharmaco-treatment available. Recently, lipids, and particularly sphingolipids, have been considered as new mediators in the pathogenic pathways and as possible therapeutic targets for the treatment of addictive states. In our review, we discuss the contribution of sphingolipids in the development of addictive states including alcohol consumption, nicotine, amphetamine, morphine, and cocaine dependencies. Recent data show that the involvement of various classes of sphingolipids, such as sphingomyelins, ceramides, globosides, sulfatides, and cerebrosides, might explain the development of some specific features of addictive states, for example, apoptotic neurodegeneration induced by psychoactive substances. On the other hand, protective effects of sphingolipids are discussed. Sphingolipids might be a key mechanism in the development of beneficial effects of moderate alcohol consumption. Therefore, sphingolipid systems emerge as possible new pathways involved in the development of addiction and its pathophysiological consequences. However, further analysis is still needed to investigate the exact mechanisms of sphingolipid contribution and possibility of using of sphingolipids as new therapeutic targets.

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Abbreviations

alkSM:

Alkaline sphingomyelinase

AMPK:

AMP-activated protein kinase

ASM:

Acid sphingomyelinase

ASM KO:

ASM knockout mice

BDNF:

Brain-derived neurotrophic factor

C1P:

Ceramide-1-phosphate

cAMP:

Cyclic adenosine monophosphate

Cer:

Ceramide

CerD:

Ceramidase

CerS:

Ceramide synthases

CST:

Cerebroside sulfotransferase

ER:

Endoplasmic reticulum

FIASMA:

Functional inhibitor of ASM

GluCer:

Glucosylceramide

GSL:

Glycosphingolipids

IL:

Interleukin

LacCer:

Lactosylceramide

NADPH:

Nicotinamide adenine dinucleotide phosphate

NMDA:

N-methyl-d-aspartate

NNK:

Nicotine-derived nitrosamine ketone

NSM:

Neutral sphingomyelinase

S1P:

Sphingosine-1-phosphate

Scd-1:

Stearoyl-CoA desaturase-1

SK:

Sphingosine kinase

SL:

Sphingolipids

SM:

Sphingomyelin

SMPD:

Sphingomyelin phosphodiesterase

SMS:

Sphingomyelin synthase

SPL:

Sphingosine-1-phosphate lyase

SPP:

Sphingosine-1-phosphate phosphatase

SPT:

Serine palmitoyltransferase

ST:

Sulfatides

tgASM:

Transgenic mice with ASM hyperactivity

TNFα:

Tumor necrosis factor α

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Acknowledgements

This work was supported by funding from DFG Grants MU 2789/8-1 (C.P.M.), KO 947/15-1, KO 947/13-1 (J.K.), and GU 335/29-1 (E.G.) and by funding from the Interdisciplinary Center for Clinical Research (IZKF) Erlangen, Project E13 (L.S.K., C.P.M., J.K.).

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Authors and Affiliations

  1. Section of Addiction Medicine, Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Liubov S. Kalinichenko, Johannes Kornhuber & Christian P. Müller

  2. Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany

    Erich Gulbins

  3. Department of Surgery, University of Cincinnati, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267-0558, USA

    Erich Gulbins

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  1. Liubov S. Kalinichenko
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  2. Erich Gulbins
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  4. Christian P. Müller
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Correspondence to Christian P. Müller.

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Kalinichenko, L.S., Gulbins, E., Kornhuber, J. et al. The role of sphingolipids in psychoactive drug use and addiction. J Neural Transm 125, 651–672 (2018). https://doi.org/10.1007/s00702-018-1840-1

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