Deletion of the vesicular monoamine transporter 1 (vmat1/slc18a1) gene affects dopamine signaling

•VMAT1 has recently been identified as target for neuropsychiatric disorders.•This study investigated null-mutant VMAT1 animals for effects on monoamine signaling and behavior.•VMAT1 KO mice show a marked behavioral locomotor response when treated with amphetamine.•Dopaminergic signaling is robustly...

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Bibliographic Details
Published in:Brain research 2019-06, Vol.1712, p.151-157
Main Authors: Lohoff, Falk W., Carr, Gregory V., Brookshire, Bethany, Ferraro, Thomas N., Lucki, Irwin
Format: Article
Language:English
Subjects:
Addiction
Bipolar disorder
DAT
Dopamine
Schizophrenia
SLC18A1
VMAT2
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Summary:•VMAT1 has recently been identified as target for neuropsychiatric disorders.•This study investigated null-mutant VMAT1 animals for effects on monoamine signaling and behavior.•VMAT1 KO mice show a marked behavioral locomotor response when treated with amphetamine.•Dopaminergic signaling is robustly altered in the frontal cortex of VMAT1 null-mutant mice. The vesicular monoamine transporter is involved in presynaptic catecholamine storage and neurotransmission. Two isoforms of the transporter exist, VMAT1 and VMAT2, and both are expressed in the brain, though VMAT2 expression is more robust and has been more widely studied. In this study we investigated the role of VMAT1 KO on markers of dopaminergic function and neurotransmission, and dopamine-related behaviors. Null-mutant VMAT1 mice were studied behaviorally using the tail suspension test, elevated zero maze and locomotor activity assessments. Tissue monoamines were measured both ex vivo and by using in vivo microdialysis. Protein expression of tyrosine hydroxylase and D2 dopamine receptors was measured using western blot analysis. Results show that VMAT1 KO mice have decreased dopamine levels in the frontal cortex, increased postsynaptic D2 expression, and lower frontal cortex tyrosine hydroxylase expression compared to WT mice. VMAT1 KO mice also show an exaggerated behavioral locomotor response to acute amphetamine treatment. We conclude that dopaminergic signaling is robustly altered in the frontal cortex of VMAT1 null-mutant mice and suggest that VMAT1 may be relevant to the pathogenesis and/or treatment of psychiatric illnesses including schizophrenia and bipolar disease.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2019.01.029