The role of sphingolipids in psychoactive drug use and addiction

  • Liubov S. Kalinichenko
  • Erich Gulbins
  • Johannes Kornhuber
  • Christian P. Müller
High Impact Review in Neuroscience, Neurology or Psychiatry - Review Article

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.

Keywords

Addiction Lipids Sphingolipids Neuroapoptosis Protective properties 

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

Notes

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.).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Liubov S. Kalinichenko
    • 1
  • Erich Gulbins
    • 2
    • 3
  • Johannes Kornhuber
    • 1
  • Christian P. Müller
    • 1
  1. 1.Section of Addiction Medicine, Department of Psychiatry and Psychotherapy, University ClinicFriedrich-Alexander-University of Erlangen-NurembergErlangenGermany
  2. 2.Department of Molecular BiologyUniversity of Duisburg-EssenEssenGermany
  3. 3.Department of SurgeryUniversity of Cincinnati, College of MedicineCincinnatiUSA

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