Deletion of the vesicular monoamine transporter 1 (vmat1/slc18a1) gene affects dopamine signaling
Autor: | Bethany R. Brookshire, Gregory V. Carr, Falk W. Lohoff, Thomas N. Ferraro, Irwin Lucki |
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Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Tyrosine 3-Monooxygenase Dopamine Vesicular monoamine transporter 1 Biology Synaptic Transmission Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Amphetamine Molecular Biology Mice Knockout Dopamine Plasma Membrane Transport Proteins Tyrosine hydroxylase Mental Disorders General Neuroscience Dopaminergic Frontal Lobe Vesicular monoamine transporter 030104 developmental biology Monoamine neurotransmitter Endocrinology chemistry Vesicular Monoamine Transport Proteins Catecholamine Neurology (clinical) 030217 neurology & neurosurgery Signal Transduction Developmental Biology medicine.drug |
Zdroj: | Brain Research. 1712:151-157 |
ISSN: | 0006-8993 |
Popis: | 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. |
Databáze: | OpenAIRE |
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