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VGLUT3 gates psychomotor effects induced by amphetamine
Nina Mansouri-Guilani1, Véronique Bernard1, Erika Vigneault1
1Neuroscience ParisSeine - Institut de Biologie Paris Seine (NPS - IBPS) INSERM, CNRS, Sorbonne Université, Paris, France.
Journal of Neurochemistry
|December 18, 2018
Summary
Vesicular glutamate transporter 3 (VGLUT3) in cholinergic neurons, not serotonergic, influences amphetamine
Area of Science:
- Neuroscience
- Neuropharmacology
- Molecular Biology
Background:
- Modulatory neurons co-express vesicular glutamate transporters (VGLUTs) alongside other transporters, suggesting novel communication pathways.
- Vesicular glutamate transporter 3 (VGLUT3) is found in striatal cholinergic interneurons (TANs) and 5-HT fibers, implicated in amphetamine's psychomotor effects.
- The role of VGLUT3-mediated glutamate co-transmission in psychostimulant-induced behaviors remains largely unexplored.
Purpose of the Study:
- To investigate the involvement of VGLUT3 and glutamate co-transmission in amphetamine-induced psychomotor effects and stereotypies.
- To determine if VGLUT3 expression in specific neuronal populations gates behavioral responses to amphetamine.
Main Methods:
- Utilized constitutive and cell-type specific VGLUT3-deficient mouse lines.
- Administered acute and chronic amphetamine to assess psychomotor activity (locomotor activity, stereotypies).
- Measured striatal ∆FosB expression as a marker of chronic drug exposure.
- Examined VGLUT3 deletion specifically in serotonergic and cholinergic neurons.
Main Results:
- VGLUT3-null mice exhibited blunted amphetamine-induced stereotypies and reduced striatal ∆FosB expression.
- Deletion of VGLUT3 in serotonergic neurons did not alter amphetamine sensitivity.
- Specific deletion of VGLUT3 in cholinergic neurons partially mimicked the effects of constitutive VGLUT3 knockout.
- Constitutive VGLUT3 deletion modulated both acute and chronic locomotor responses to amphetamine.
Conclusions:
- VGLUT3 expression in cholinergic neurons, not serotonergic, is critical for mediating amphetamine-induced psychomotor effects and stereotypies.
- VGLUT3 plays a pivotal role in gating psychomotor adaptations induced by amphetamine, highlighting its importance in neurochemical signaling.
- Findings underscore the significance of VGLUT3 in multiple brain areas for regulating responses to psychostimulants.
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