VGLUT3 gates psychomotor effects induced by amphetamine. Issue 6 (15th January 2019)

• Record Type: Journal Article
• Authors: Mansouri‐Guilani, Nina; Bernard, Véronique; Vigneault, Erika; Vialou, Vincent; Daumas, Stéphanie; El Mestikawy, Salah; Gangarossa, Giuseppe
• Is Part Of: Journal of neurochemistry. Volume 148:Issue 6(2019)
• Page Start: 779
• Page End: 795
• Publication Date: 2019-01-15
• Subjects: amphetamine -- cholinergic interneurons (TANs) -- dorsal striatum -- glutamate -- stereotypies -- vesicular glutamate transporter type 3 (VGLUT3); Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14644
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Several subtypes of modulatory neurons co‐express vesicular glutamate transporters (VGLUTs) in addition to their cognate vesicular transporters. These neurons are believed to establish new forms of neuronal communication. The atypical VGLUT3 is of particular interest since in the striatum this subtype is found in tonically active cholinergic interneurons (TANs) and in a subset of 5‐HT fibers. The striatum plays a major role in psychomotor effects induced by amphetamine. Whether and how VGLUT3‐operated glutamate/ACh or glutamate/5HT co‐transmissions modulates psychostimulants‐induced maladaptive behaviors is still unknown. Here, we investigate the involvement of VGLUT3 and glutamate co‐transmission in amphetamine‐induced psychomotor effects and stereotypies. Taking advantage of constitutive and cell‐type specific VGLUT3‐deficient mouse lines, we tackled the hypothesis that VGLUT3 could gate psychomotor effects (locomotor activity and stereotypies) induced by acute or chronic administration of amphetamine. Interestingly, VGLUT3‐null mice demonstrated blunted amphetamine‐induced stereotypies as well as reduced striatal ∆FosB expression. VGLUT3‐positive varicosities within the striatum arise in part from 5HT neurons. We tested the involvement of VGLUT3 deletion in serotoninergic neurons in amphetamine‐induced stereotypies. Mice lacking VGLUT3 specifically in 5HT fibers showed no alteration to amphetamine sensitivity. In contrast, specific deletion of VGLUT3 in cholinergic neurons partially phenocopied the effects observed in the constitutive knock‐out mice. Our results show that constitutive deletion of VGLUT3 modulates acute and chronic locomotor effects induced by amphetamine. They point to the fact that the expression of VGLUT3 in multiple brain areas is pivotal in gating amphetamine‐induced psychomotor adaptations. Open Science Badges: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found athttps://cos.io/our-services/open-science-badges/ . Abstract : VGLUT3 is detected in neurons that use other neurotransmitters than glutamate, a neurochemical feature known as vesicular synergy. Here, we investigate the involvement of VGLUT3 in amphetamine‐induced psychomotor effects. We found that deletion of VGLUT3 promoted hyperlocomotor responses whereas blunted stereotypies were observed following amphetamine administration. A reduced expression of ∆FosB in the striatum mirrored such phenotype. In the striatum, VGLUT3 is expressed in cholinergic neurons and 5HT fibers. Cell‐type specific deletion of VGLUT3 in ACh and 5HT neurons revealed a complex dynamic regulation of amphetamine‐related effects. Our study points VGLUT3 as a critical modulator of psychostimulants‐induced adaptations. Open Science: This manuscript was awarded with the Open Materials Badge For more information see:https://cos.io/our-services/open-science-badges/