Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way
Addiction is a chronic and severe mental disorder with high gender- and sex-specificity. However, the pathogenesis of this disorder is not fully elucidated, and no targeted pharmacotherapy is available. A growing body of evidence points out the potential involvement of the ceramide system in the pat...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000166 |
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| author | Liubov S. Kalinichenko Iulia Zoicas Anne-Marie Bienia Clara Bühner Julia Robinson Joshua Kütemeyer Annika Labonte Thadshajiny Raveendran Lena Warth Irena Smaga Malgorzata Filip Volker Eulenburg Cosima Rhein Anna Fejtova Erich Gulbins Johannes Kornhuber Christian P. Müller |
| author_facet | Liubov S. Kalinichenko Iulia Zoicas Anne-Marie Bienia Clara Bühner Julia Robinson Joshua Kütemeyer Annika Labonte Thadshajiny Raveendran Lena Warth Irena Smaga Malgorzata Filip Volker Eulenburg Cosima Rhein Anna Fejtova Erich Gulbins Johannes Kornhuber Christian P. Müller |
| author_sort | Liubov S. Kalinichenko |
| collection | DOAJ |
| description | Addiction is a chronic and severe mental disorder with high gender- and sex-specificity. However, the pathogenesis of this disorder is not fully elucidated, and no targeted pharmacotherapy is available. A growing body of evidence points out the potential involvement of the ceramide system in the pathophysiology of addiction. A pathogenic pathway for several mental disorders based on the overexpression of an enzyme involved in ceramide formation, acid sphingomyelinase (ASM), was recently proposed. Here we show a crucial role of ASM specifically overexpressing in the forebrain for various types of addiction-related behaviours in a drug- and sex-specific way. In male mice, a forebrain ASM overexpression led to enhanced alcohol consumption in a free-choice paradigm. It also diminished the reinforcing properties of alcohol and cocaine, but not that of amphetamine, ketamine, or a natural reinforcer fat/carbohydrate-rich food in the conditioned place preference (CPP) test in males. In female mice, a forebrain ASM overexpression enhanced alcohol binge-like drinking, while moderate alcohol consumption was preserved. ASM overexpression in females contributed to CPP establishment for amphetamine, but not for other psychoactive substances. Altogether, this study shows a specific involvement of forebrain ASM in the development of conditioned reinforcing effects of different types of substances with addictive properties in a sex-specific way. Our data enlarge the current knowledge on the specific molecular mechanisms of dependence from various drugs of abuse and might serve as a basis for the development of drug- and sex-specific targeted therapy. |
| format | Article |
| id | doaj-art-e7ce34f5ee424a56b4011a43c00dd788 |
| institution | DOAJ |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-e7ce34f5ee424a56b4011a43c00dd7882025-08-20T03:00:24ZengElsevierNeurobiology of Disease1095-953X2025-03-0120610680010.1016/j.nbd.2025.106800Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific wayLiubov S. Kalinichenko0Iulia Zoicas1Anne-Marie Bienia2Clara Bühner3Julia Robinson4Joshua Kütemeyer5Annika Labonte6Thadshajiny Raveendran7Lena Warth8Irena Smaga9Malgorzata Filip10Volker Eulenburg11Cosima Rhein12Anna Fejtova13Erich Gulbins14Johannes Kornhuber15Christian P. Müller16Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany; Corresponding author.Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyMaj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Smętna 12, 31-343 Kraków, PolandMaj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Smętna 12, 31-343 Kraków, PolandDepartment for Translational Anaesthesiology and Intensive Care Medicine, Medical Faculty University of Augsburg, Stenglinstr. 2, 86156 Augsburg, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyInstitute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany; Institute of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, J 5, 68159 Heidelberg, GermanyAddiction is a chronic and severe mental disorder with high gender- and sex-specificity. However, the pathogenesis of this disorder is not fully elucidated, and no targeted pharmacotherapy is available. A growing body of evidence points out the potential involvement of the ceramide system in the pathophysiology of addiction. A pathogenic pathway for several mental disorders based on the overexpression of an enzyme involved in ceramide formation, acid sphingomyelinase (ASM), was recently proposed. Here we show a crucial role of ASM specifically overexpressing in the forebrain for various types of addiction-related behaviours in a drug- and sex-specific way. In male mice, a forebrain ASM overexpression led to enhanced alcohol consumption in a free-choice paradigm. It also diminished the reinforcing properties of alcohol and cocaine, but not that of amphetamine, ketamine, or a natural reinforcer fat/carbohydrate-rich food in the conditioned place preference (CPP) test in males. In female mice, a forebrain ASM overexpression enhanced alcohol binge-like drinking, while moderate alcohol consumption was preserved. ASM overexpression in females contributed to CPP establishment for amphetamine, but not for other psychoactive substances. Altogether, this study shows a specific involvement of forebrain ASM in the development of conditioned reinforcing effects of different types of substances with addictive properties in a sex-specific way. Our data enlarge the current knowledge on the specific molecular mechanisms of dependence from various drugs of abuse and might serve as a basis for the development of drug- and sex-specific targeted therapy.http://www.sciencedirect.com/science/article/pii/S0969996125000166Acid sphingomyelinaseForebrainAddictionConditioned place preferenceAlcoholCocaine |
| spellingShingle | Liubov S. Kalinichenko Iulia Zoicas Anne-Marie Bienia Clara Bühner Julia Robinson Joshua Kütemeyer Annika Labonte Thadshajiny Raveendran Lena Warth Irena Smaga Malgorzata Filip Volker Eulenburg Cosima Rhein Anna Fejtova Erich Gulbins Johannes Kornhuber Christian P. Müller Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way Neurobiology of Disease Acid sphingomyelinase Forebrain Addiction Conditioned place preference Alcohol Cocaine |
| title | Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way |
| title_full | Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way |
| title_fullStr | Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way |
| title_full_unstemmed | Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way |
| title_short | Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way |
| title_sort | brain acid sphingomyelinase controls addiction related behaviours in a sex specific way |
| topic | Acid sphingomyelinase Forebrain Addiction Conditioned place preference Alcohol Cocaine |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000166 |
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