title: The activation of metabotropic glutamate 5 receptors in the rat ventral tegmental area increases dopamine extracellular levels.
abstract: The mesocorticolimbic circuit projects to the prefrontal cortex, hippocampus, amygdala, and nucleus accumbens, among others, and it originates in the dopaminergic neurons of the ventral tegmental area (VTA). The VTA receives glutamatergic inputs from the prefrontal cortex and several subcortical regions. The glutamate released activates dopaminergic neurons and its action depends on the activation of ionotropic and metabotropic glutamate receptors. VTA dopaminergic neurons release dopamine (DA) from axon terminals in the innervated regions and somatodendritically in the VTA itself. DA release in the VTA is directly correlated with the activity of dopaminergic neurons. We hypothesized that metabotropic glutamate 5 receptors (mGlu5) directly regulate the activity of VTA dopaminergic neurons. To test this hypothesis, the extracellular levels of VTA DA and glutamate were studied by in-vivo microdialysis after an intra-VTA perfusion of (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), selective mGlu5 agonist. We observed that CHPG induced a significant increase in VTA DA and glutamate extracellular levels. To determine whether the effect of CHPG on DA levels is because of the increase in glutamate release, we perfused kynurenic acid, an ionotropic glutamate receptor antagonist, through the probe. Our results showed that kynurenic acid did not block the ability of CHPG to cause DA release. Thus, our results suggest that CHPG acts directly on mGlu5 in dopaminergic neurons to induce the release of DA.
authors.affiliation: aLaboratory of Cellular and Molecular Biology of Addiction, Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago bLaboratory of Neurochemistry and Neuropharmacology, Center of Neurobiology and Brain Plasticity, Institute of Physiology, Faculty of Biological Sciences, Universidad de Valparaíso, Chile.
authors.forename: Carla
authors.initials: C
authors.lastname: Ferrada
authors.forename: Ramón
authors.initials: R
authors.lastname: Sotomayor-Zárate
authors.forename: Jorge
authors.initials: J
authors.lastname: Abarca
authors.forename: Katia
authors.initials: K
authors.lastname: Gysling
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D010648:Phenylacetates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D018683:Excitatory Amino Acid Agents; D010648:Phenylacetates; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles; D018698:Glutamic Acid; D007736:Kynurenic Acid; D005998:Glycine; D004298:Dopamine