The activation of metabotropic glutamate 5 receptors in the rat ventral tegmental area increases dopamine extracellular levels

Ferrada, Carla; Sotomayor‐Zárate, Ramón; Abarca, Jorge; Gysling, Katia

doi:10.1097/wnr.0000000000000708

Cited by 10 publications

(5 citation statements)

References 38 publications

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“…A possible mechanism is through blockage of mGlu5 in dopaminergic neurons in the ventral tegmental area (VTA). Ferrada et al (Ferrada et al 2017) reported that intra-VTA infusion of the selective mGlu5 agonist CHPG increased release of dopamine, suggesting the possibility that MPEP, acting at mGlu5 receptors in dopaminergic neurons in VTA, could reduce dopaminergic inputs to the striatum, counteracting the reduced corticostriatal glutamatergic inputs into striatum in DLX-mGlu5 KO mice, thus resulting in overall hypo-locomotion.…”

Section: Discussionmentioning

confidence: 99%

mGlu5 in GABAergic neurons modulates spontaneous and psychostimulant-induced locomotor activity

Jew

Sun

et al. 2019

Psychopharmacology

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Rationale-A role of group I metabotropic glutamate receptor 5 (mGlu5) in regulating spontaneous locomotion and psychostimulant-induced hyperactivity has been proposed.Objectives-This study aims to determine if mGlu5 in GABAergic neurons regulates spontaneous or psychostimulant-induced locomotion.Methods-We generated mice specifically lacking mGlu5 in forebrain GABAergic neuron by crossing DLX-Cre mice with mGlu5 flox/flox mice to generate DLX-mGlu5 KO mice. The locomotion of adult mice was examined in the open field assay (OFA) and home cage setting. The effects of the mGlu5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP), cocaine and methylphenidate on acute motor behaviors in DLX-mGlu5 KO and littermate control mice were assessed in OFA. Striatal synaptic plasticity of these mice was examined with field potential electrophysiological recordings.Results-Deleting mGlu5 from forebrain GABAergic neurons results in failure to induce longterm depression (LTD) in the dorsal striatum and absence of habituated locomotion in both novel and familiar settings. In a familiar environment (home cage), DLX-mGlu5 KO mice were hyperactive. In the OFA, DLX-mGlu5 KO mice exhibited initial hypo-activity, and then gradually increased their locomotion with time, resulting in no habituation response. DLX-mGlu5 KO mice

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Section: Discussionmentioning

confidence: 99%

mGlu5 in GABAergic neurons modulates spontaneous and psychostimulant-induced locomotor activity

Jew

Sun

et al. 2019

Psychopharmacology

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“…Increased glutamate signaling may play a role in a tuning of the VTA, since activation of glutamate receptors modulates firing of dopaminergic neurons and regulates extracellular DA levels (Ferrada et al 2017;Floresco et al 2003;Lodge and Grace 2006;Oakman et al 1995).…”

Section: Vta and Snc Transcriptomes Respond Distinctly To Da Deficiencymentioning

confidence: 99%

Transcriptome responses to reduced dopamine in the Substantia Nigra Pars Compacta reveals a potential protective role for dopamine

Koltun

Cichewicz

Gibbs

et al. 2018

Preprint

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Parkinson's Disease (PD), is a neurodegenerative disorder affecting both cognitive and motor functions. It is characterized by decreased brain dopamine (DA) and a selective and progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), whereas dopaminergic neurons in the ventral tegmental area (VTA) show reduced vulnerability. The majority of animal models of PD are genetic lesion or neurotoxin exposure models that lead to death of dopaminergic neurons. Here we use a DAT:TH KO mouse model that by inactivation of the tyrosine hydroxylase (Th) gene in dopamine transporter-expressing neurons, causes selective depletion of striatal dopamine without affecting DA neuron survival. We analyzed transcriptome responses to decreased DA in both pre-and post-synaptic dopaminergic brain regions of DAT:TH KO animals. We detected only few differentially expressed genes in the post-synaptic regions as a function of DA deficiency. This suggests that the broad striatal transcriptional changes in neurodegeneration-based PD models are not direct effects of DA depletion, but are rather a result of DA neuronal death. However, we find a number of dopaminergic genes differentially expressed in SNc, and to a lesser extent in VTA, as a function of DA deficiency, providing evidence for a DA-dependent feedback loop. Of particular interest, expression of Nr4a2, a crucial transcription factor maintaining DA neuron identity, is significantly decreased in SNc, but not VTA, of DAT:TH KO mice, implying a potential protective role for DA in the SNc.

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“…GLU and GABA quantifications: experimental conditions were as described previously [ 28 , 29 ]. Briefly, 20 μL of each cleaned supernatant was mixed with 4 μL of borate buffer (pH 10.8), and then the mixture was derivatized by adding 4 μL of fluorogenic reagent (20 mg of orthophthaldehyde and 10 μL of β-mercaptoethanol in 5 mL of ethanol).…”

Section: Methodsmentioning

confidence: 99%

Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice

et al. 2017

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BackgroundObsessive–compulsive disorder (OCD) is a severe neuropsychiatric condition affecting 1–3% of the worldwide population. OCD has a strong genetic component, and the SLC1A1 gene that encodes neuronal glutamate transporter EAAT3 is a strong candidate for this disorder. To evaluate the impact of reduced EAAT3 expression in vivo, we studied male EAAT3 heterozygous and wild-type littermate mice using a battery of behavioral paradigms relevant to anxiety (open field test, elevated plus maze) and compulsivity (marble burying), as well as locomotor activity induced by amphetamine. Using high-performance liquid chromatography, we also determined tissue neurotransmitter levels in cortex, striatum and thalamus—brain areas that are relevant to OCD.ResultsCompared to wild-type littermates, EAAT3 heterozygous male mice have unaltered baseline anxiety-like, compulsive-like behavior and locomotor activity. Administration of acute amphetamine (5 mg/kg intraperitoneally) increased locomotion with no differences across genotypes. Tissue levels of glutamate, GABA, dopamine and serotonin did not vary between EAAT3 heterozygous and wild-type mice.ConclusionsOur results indicate that reduced EAAT3 expression does not impact neurotransmitter content in the corticostriatal circuit nor alter anxiety or compulsive-like behaviors.Electronic supplementary materialThe online version of this article (doi:10.1186/s40659-017-0138-3) contains supplementary material, which is available to authorized users.

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The activation of metabotropic glutamate 5 receptors in the rat ventral tegmental area increases dopamine extracellular levels

Cited by 10 publications

References 38 publications

mGlu5 in GABAergic neurons modulates spontaneous and psychostimulant-induced locomotor activity

mGlu5 in GABAergic neurons modulates spontaneous and psychostimulant-induced locomotor activity

Transcriptome responses to reduced dopamine in the Substantia Nigra Pars Compacta reveals a potential protective role for dopamine

Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice

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