Endogenous Glutamate Increases Extracellular Concentrations of Dopamine, GABA, and Taurine Through NMDA and AMPA/Kainate Receptors in Striatum of the Freely Moving Rat: A Microdialysis Study

Segovia, Gregorio; Arco, Alberto Del; Mora, Francisco

doi:10.1046/j.1471-4159.1997.69041476.x

Cited by 118 publications

(65 citation statements)

References 31 publications

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“…Although it is tempting to speculate that some differences observed in the Glu in the dorsal caudate may be related to the dopaminergic tone, our study was not designed to address this question. Although, in agreement with our results, preclinical studies have shown that elevation in striatal endogenous Glu induces an increase in striatal dopamine release (Segovia et al, 1997). Preliminary results from our group (de la Fuente-Sandoval et al, 2009) have shown that patients with schizophrenia during an acute psychotic episode and after 6 weeks of antipsychotic treatment presented with higher Glu levels in the dorsal caudate compared with controls, and with no differences in the cerebellum.…”

Section: Summary Of Main Resultssupporting

confidence: 92%

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Fuente‐Sandoval

León-Ortíz

Favila

et al. 2011

Neuropsychopharmacol

208

157

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The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy ( 1 H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first-episode psychosis patients (FEP), and (3) 40 age-and sex-matched healthy controls. All subjects underwent a 1 H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia.

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Section: Summary Of Main Resultssupporting

confidence: 92%

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Fuente‐Sandoval

León-Ortíz

Favila

et al. 2011

Neuropsychopharmacol

208

157

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“…Another possibility that could explain the relatively selective effect of MLA on the protection against the long-term decreases in markers of DA compared with 5-HT terminals is the differential expression of calcium-permeable NMDA and AMPA receptors on dopaminergic and serotonergic terminals. There is evidence of calcium-permeable NMDA and AMPA receptors on striatal DA terminals (Segovia et al, 1997;Herná ndez et al, 2003) but less evidence of their expression on 5-HT terminals. However, there are studies indicating that both DA and 5-HT neurons are susceptible to excitotoxic damage in response to excess glutamate (Storey et al, 1992;Staszewski and Yamamoto, 2006).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Glutamate Release by α7 Nicotinic Receptors: Differential Role in Methamphetamine-Induced Damage to Dopaminergic and Serotonergic Terminals

Northrop

Smith

Yamamoto

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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Regulation of glutamate release is an important underlying mechanism in mediating excitotoxic events such as damage to dopamine (DA) and serotonin (5-HT) neurons observed after exposure to methamphetamine (Meth). One way to regulate glutamate release may be through the modulation of ␣7 nicotinic acetylcholine (nACh) receptors. Meth administration is known to increase acetylcholine release; however, it is unknown whether Meth increases glutamate release and causes long-term damage to both DA and 5-HT terminals through the activation of ␣7 nACh receptors. To test this hypothesis, the ␣7 nACh receptor antagonist, methyllycaconitine (MLA), was administered before the administration of repeated doses of Meth while simultaneously monitoring extracellular striatal glutamate with in vivo microdialysis. In addition, the subsequent longterm decreases in markers of dopaminergic and serotonergic terminals, including DA reuptake transporter (DAT), serotonin reuptake transporter (SERT), vesicular monoamine transporter-2, vesicular DA, and vesicular 5-HT content in the rat striatum, were measured. The results show that MLA pretreatment prevented Meth-induced increases in striatal glutamate and protected against the subsequent long-term decreases in striatal DAT and vesicular DA content without affecting the hyperthermia produced by Meth. In contrast, the Meth-induced decreases in striatal SERT immunoreactivity and vesicular 5-HT content were not affected by MLA. This suggests that the ␣7 nACh receptor differentially mediates glutamate-dependent damage to DA but not 5-HT terminals in a manner that is independent of hyperthermia. Furthermore, antagonism of ␣7 nACh receptors may be a possible therapeutic strategy for decreasing extracellular glutamate and preventing the excitotoxic damage observed in other DA-related neurodegenerative disorders.

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“…4, the increases of acetylcholine, but not DOPAC and HVA, produced by local injections into the PFC of CPP (1 μg/0.5 μL) were blocked by the (Segovia et al 1997a). …”

Section: Effects Of Cpp Injected Into the Pfc On Extracellular Concenmentioning

confidence: 84%

Blockade of NMDA receptors in the prefrontal cortex increases dopamine and acetylcholine release in the nucleus accumbens and motor activity

2008

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Endogenous Glutamate Increases Extracellular Concentrations of Dopamine, GABA, and Taurine Through NMDA and AMPA/Kainate Receptors in Striatum of the Freely Moving Rat: A Microdialysis Study

Cited by 118 publications

References 31 publications

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Regulation of Glutamate Release by α7 Nicotinic Receptors: Differential Role in Methamphetamine-Induced Damage to Dopaminergic and Serotonergic Terminals

Blockade of NMDA receptors in the prefrontal cortex increases dopamine and acetylcholine release in the nucleus accumbens and motor activity

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