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Behav Brain Res. 2019 Feb 6. pii: S0166-4328(19)30062-2. doi: 10.1016/j.bbr.2019.02.011. [Epub ahead of print]

Behavioral and metabolic effects of S-adenosylmethionine and imipramine in the Flinders Sensitive Line rat model of depression.

Author information

1
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark. Electronic address: sti@clin.au.dk.
2
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, DK-8240 Risskov, Denmark.
3
Saarland University Hospital, Department of Clinical Chemistry and Laboratory Medicine, Building 57, D-66421 Homburg, Saar, Germany.
4
Saarland University Hospital, Department of Clinical Chemistry and Laboratory Medicine, Building 57, D-66421 Homburg, Saar, Germany; Aarhus Institute of Advanced Studies, Aarhus University, DK-8000 Aarhus C, Denmark.

Abstract

Depression is associated with dysregulation of methyl group metabolism such as low S-adenosylmethionine (SAM). We previously reported that Flinders Sensitive Line (FSL) rats, an animal model of depression, had lower concentrations of liver SAM than the control rats, Flinders Resistant Line (FRL) rats. The present study investigated if SAM supplementation may correct liver SAM and behavioral abnormalities in this model. Moreover, we compared one-carbon (C1) metabolites, neurotransmitters, and gastrointestinal (GI) transit in SAM-treated versus imipramine (IMI)-treated animals. FSL rats received vehicle, IMI, SAM, or IMI + SAM (n = 9-10 per group) once daily through oral gavage for 4 weeks; FRL rats received vehicle. Behavior was assessed using standard tests for locomotion, cognition, and depressive-like behavior. Monoamine neurotransmitters and C1 metabolites were measured using UHPLC-ECD and UPLC-MS/MS, respectively. Compared to FRL rats, FSLs had lower liver SAM, higher plasma serotonin, lower hippocampal dopamine and serotonin turnover, and faster GI transit. Behaviorally, FSL rats showed impaired cognitive performance as well as increased depressive-like behavior compared to FRLs. Coadministration of IMI and SAM seemed to have adverse effects on spatial memory. SAM or IMI administration did not reverse C1 metabolites, neurotransmitters, or GI transit in FSLs. Despite low liver SAM in FSL rats, orally administered SAM did not show antidepressant effects in this specific animal model of depression.

KEYWORDS:

Depression; Flinders Sensitive Line rats; Imipramine; One-Carbon Metabolism; S-adenosylmethionine

PMID:
30738101
DOI:
10.1016/j.bbr.2019.02.011

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