ArticleActa neuropathologica2017
Paradoxical antidepressant effects of alcohol are related to acid sphingomyelinase and its control of sphingolipid homeostasis.
Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Self-management with alcohol over lifespan: psychological mechanisms, neurobiological underpinnings, and risk assessment.Molecular psychiatry · 2023Pooled it
- The role of sphingolipids in major depressive disorder and associated cognitive impairment: interactions with monoaminergic signaling, neuroinflammation, and neurogenesis.Molecular psychiatry · 2026Review
- Sphingolipids in Emotional Well-Being.Journal of neurochemistry · 2026Review
- Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.Molecular psychiatry · 2025Article
- Exercise improves depressive-like behavior in adolescent mice by regulating sphingosine and ceramide metabolism through microglial CerS1.Communications biology · 2025Article
- Neuroprotection vs. Neurotoxicity: The Dual Impact of Brain Lipids in Depression.International journal of molecular sciences · 2025Review
- Serotonin Signaling through Lipid Membranes.ACS chemical neuroscience · 2024Review
- Masculine depression and its problem behaviors: use alcohol and drugs, work hard, and avoid psychiatry!European archives of psychiatry and clinical neuroscience · 2024Article
- Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis.Frontiers in public health · 2024Article
- Article
- Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models.Psychopharmacology · 2023Article
- Acid Sphingomyelinase Is a Modulator of Contextual Fear.International journal of molecular sciences · 2022Article
- Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects.Molecular psychiatry · 2021Article
- Neutral ceramidase is a marker for cognitive performance in rats and monkeys.Pharmacological reports : PR · 2021Article
- A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS.The Journal of experimental medicine · 2021Article
- Impact of Alcohol Abuse on Susceptibility to Rare Neurodegenerative Diseases.Frontiers in molecular biosciences · 2021Review
- Adolescent Alcohol Exposure Produces Protracted Cognitive-Behavioral Impairments in Adult Male and Female Rats.Brain sciences · 2020Article
- The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice.Cells · 2020Article
- Anxiety and Depression Are Related to Higher Activity of Sphingolipid Metabolizing Enzymes in the Rat Brain.Cells · 2020Article
- Transcriptome Analysis of Alcohol Drinking in Non-Dependent and Dependent Mice Following Repeated Cycles of Forced Swim Stress Exposure.Brain sciences · 2020Article
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alcohol is a widely consumed drug that can lead to addiction and severe brain damage. However, alcohol is also used as self-medication for psychiatric problems, such as depression, frequently resulting in depression-alcoholism comorbidity. Here, we identify the first molecular mechanism for alcohol use with the goal to self-medicate and ameliorate the behavioral symptoms of a genetically induced innate depression. An induced over-expression of acid sphingomyelinase (ASM), as was observed in depressed patients, enhanced the consumption of alcohol in a mouse model of depression. ASM hyperactivity facilitates the establishment of the conditioned behavioral effects of alcohol, and thus drug memories. Opposite effects on drinking and alcohol reward learning were observed in animals with reduced ASM function. Importantly, free-choice alcohol drinking-but not forced alcohol exposure-reduces depression-like behavior selectively in depressed animals through the normalization of brain ASM activity. No such effects were observed in normal mice. ASM hyperactivity caused sphingolipid and subsequent monoamine transmitter hypo-activity in the brain. Free-choice alcohol drinking restores nucleus accumbens sphingolipid- and monoamine homeostasis selectively in depressed mice. A gene expression analysis suggested strong control of ASM on the expression of genes related to the regulation of pH, ion transmembrane transport, behavioral fear response, neuroprotection and neuropeptide signaling pathways. These findings suggest that the paradoxical antidepressant effects of alcohol in depressed organisms are mediated by ASM and its control of sphingolipid homeostasis. Both emerge as a new treatment target specifically for depression-induced alcoholism.
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