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

Highlights

• Vesicular monoamine transporters are involved in presynaptic catecholamine storage and contribute to monoamine neurotransmission.
• Two isoforms exist, VMAT1 and VMAT2, but limited data exist for VMAT1.
• VMAT1 has recently been identified as target for neuropsychiatric disorders.
• This study investigated null-mutant VMAT1 animals for effects on monoamine tissue content, effects on up- and downstream dopaminergic targets and behavioral consequences.
• VMAT1 KO mice have decreased dopamine levels in frontal cortex, increased postsynaptic DRD2 expression and lower frontal cortex tyrosine hydroxylase expression.
• VMAT1 KO mice show a marked behavioral locomotor response when challenged with amphetamine.

Abstract

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.

 

Link to the publication :

https://www.sciencedirect.com/science/article/pii/S0006899319300459