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Abstract
Depression and alcohol dependence are associated with increased plasma ceramide concentrations in humans. Pharmacological increase in C16 ceramide concentrations in the dorsal hippocampus (DH) induced a depressive-like phenotype in naïve mice. However, the effects of C16 ceramide on alcohol consumption and anxiety-like behavior as well as the behavioral effects of other ceramide species are yet unknown. Therefore, we investigated whether repeated infusion of ceramides with different fatty acid chain lengths (C8, C16, and C20) into the DH and the basolateral amygdala (BLA) alter alcohol consumption, emotional behavior, and tissue monoamine levels. Our results revealed that C16, but not C8 and C20, ceramide altered alcohol drinking and emotional behavior in a brain region-specific way without altering tissue noradrenaline, dopamine, and serotonin levels in the prefrontal cortex, ventral striatum, and dorsal mesencephalon. In more detail, C16 ceramide increased alcohol consumption when infused into the BLA, but not when infused into the DH. Furthermore, C16 ceramide induced a depressive-like phenotype when infused into the DH, but a predominantly anxiogenic-like phenotype (in a non-social, but not a social context) when infused into the BLA. In turn, alcohol drinking normalized C16 ceramide-induced depressive-like and anxiogenic-like phenotypes. This study demonstrates a complex ceramide species-specific and brain region-specific modulation of alcohol consumption and emotional behavior in mice and provides the framework for future studies investigating the involvement of distinct ceramide species in the regulation of emotional behavior.
Highlights
Ceramides are sphingolipids composed of sphingosine and a fatty acid
C16 ceramide induced a depressive‐like phenotype when infused into the dorsal hippocampus (DH), but a predominantly anxiogenic‐like phenotype when infused into the basolateral amygdala (BLA)
The present study demonstrates for the first time that ceramides affect alcohol consumption and depressive‐like and anxiety‐like behavior in a brain region‐ and ceramide species‐specific way
Summary
Ceramides are sphingolipids composed of sphingosine and a fatty acid. They are found in high concentrations within the lipid bilayer of cell membranes where they play important roles in membrane structure and function, and regulate many cellular processes including apoptosis, cell differentiation, and proliferation.[1]. We investigated the effects of two ceramide species with long‐chain fatty acid, which have been shown to be increased in the plasma of depressive patients,[10] i.e., C16:0 and C20:0 ceramide, and one ceramide species (C8:0) with medium‐chain fatty acid as control, on alcohol consumption, depressive‐like behavior, and social and non‐social anxiety‐like behavior. These ceramide species were infused bilaterally into the DH and basolateral amygdala (BLA), as these brain regions were involved in addiction, depressive‐ like behavior, anxiety‐like behavior, and social behavior.[18,19,20]
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