Adult alcohol drinking and emotional tone are mediated by neutral sphingomyelinase during development in males

Kalinichenko L, Mühle C, Jia T, Anderheiden F, Datz M, Eberle AL, Eulenburg V, Granzow J, Hofer MJ, Hohenschild J, Huber S, Kämpf S, Kogias G, Lacatusu L, Lugmair C, Taku SM, Meixner D, Sembritzki NK, Praetner M, Rhein C, Sauer C, Scholz J, Ulrich F, Valenta F, Weigand E, Werner M, Tay N, Mc Veigh CJ, Haase J, Wang AL, Abdel-Hafiz L, Huston JP, Smaga I, Frankowska M, Filip M, Lourdusamy A, Kirchner P, Ekici AB, Marx LM, PULIPARAMBIL SURESH N, Frischknecht R, Fejtová A, Saied EM, Arenz C, Bozec A, Wank I, Kreitz S, Heß A, Bäuerle T, Ledesma MD, Mitroi DN, Miranda AM, Oliveira TG, Lenz B, Schumann G, Kornhuber J, Müller CP (2022)

Publication Type: Journal article

Publication year: 2022


DOI: 10.1093/cercor/bhac106


Alcohol use, abuse, and addiction, and resulting health hazards are highly sex-dependent with unknown mechanisms. Previously, strong links between the SMPD3 gene and its coded protein neutral sphingomyelinase 2 (NSM) and alcohol abuse, emotional behavior, and bone defects were discovered and multiple mechanisms were identified for females. Here we report strong sex-dimorphisms for central, but not for peripheral mechanisms of NSM action in mouse models. Reduced NSM activity resulted in enhanced alcohol consumption in males, but delayed conditioned rewarding effects. It enhanced the acute dopamine response to alcohol, but decreased monoaminergic systems adaptations to chronic alcohol. Reduced NSM activity increased depression- and anxiety-like behavior, but was not involved in alcohol use for the self-management of the emotional state. Constitutively reduced NSM activity impaired structural development in the brain and enhanced lipidomic sensitivity to chronic alcohol. While the central effects were mostly opposite to NSM function in females, similar roles in bone-mediated osteocalcin release and its effects on alcohol drinking and emotional behavior were observed. These findings support the view that the NSM and multiple downstream mechanism may be a source of the sex-differences in alcohol use and emotional behavior.

Authors with CRIS profile

Liubov Kalinichenko Department of Psychiatry and Psychotherapy Christiane Mühle Medizinische Fakultät Felix Anderheiden Department of Paediatrics and Adolescent Medicine Anna-Lisa Eberle Professur für Suchtmedizin Martin Jürgen Hofer Professur für Suchtmedizin Sabine Huber Professur für Suchtmedizin Stefanie Kämpf Professur für Suchtmedizin Georgios Kogias Professur für Suchtmedizin Laura Lacatusu Professur für Suchtmedizin Doris Meixner Professur für Suchtmedizin Cosima Rhein Department of Psychiatry and Psychotherapy Christina Rothballer Department of Neurology Jessica Scholz Professur für Suchtmedizin Franziska Ulrich Professur für Suchtmedizin Florian Valenta Department of Anaesthesiology Esther Weigand Professur für Suchtmedizin Markus Werner Professur für Suchtmedizin Arif Bülent Ekici Institute of Human Genetics NEERAJA PULIPARAMBIL SURESH Department of Psychiatry and Psychotherapy Renato Frischknecht Lehrstuhl für Tierphysiologie Anna Fejtová Professur für Molekulare Psychiatrie Aline Bozec Juniorprofessur für Osteoimmunologie Isabel Wank Institut für Experimentelle und Klinische Pharmakologie und Toxikologie Silke Kreitz Lehrstuhl für Pharmakologie und Toxikologie Andreas Heß Lehrstuhl für Pharmakologie und Toxikologie Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Bernd Lenz Medizinische Fakultät Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie Peter Christian Müller Professur für Suchtmedizin

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How to cite


Kalinichenko, L., Mühle, C., Jia, T., Anderheiden, F., Datz, M., Eberle, A.-L.,... Müller, C.P. (2022). Adult alcohol drinking and emotional tone are mediated by neutral sphingomyelinase during development in males. Cerebral Cortex.


Kalinichenko, Liubov, et al. "Adult alcohol drinking and emotional tone are mediated by neutral sphingomyelinase during development in males." Cerebral Cortex (2022).

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