In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT<sub>2A</sub> receptor activation

Meller, Robert; Harrison, Paul J.; Elliott, J.M.; Sharp, Trevor

doi:10.1002/jnr.10126

Cited by 38 publications

(29 citation statements)

References 36 publications

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“…It is therefore speculated that attenuation of the increment of extracellular lactate concentrations by perospirone is attributable to the decrease in glutamate release through its antagonist activity at 5-HT 2A receptors. This idea is supported by the in vitro finding that 5-HT stimulates the efflux of glutamate from glial cells after 5-HT 2A receptor activation, suggesting a calcium-dependent mechanism (Meller et al 2002). Taken together, it is likely that perospirone attenuated the foot shock-stress induced lactate release through direct effect on astrocytes.…”

Section: Discussionmentioning

confidence: 87%

Role of 5-HT1A receptors in the modulation of stress-induced lactate metabolism in the medial prefrontal cortex and basolateral amygdala

et al. 2006

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Section: Discussionmentioning

confidence: 87%

Role of 5-HT1A receptors in the modulation of stress-induced lactate metabolism in the medial prefrontal cortex and basolateral amygdala

et al. 2006

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“…NT-3 is produced by glial cells [11,34]. 5-HT increases the release of glial glutamate [86]. Proline oxidase appears to catalyze the first step of an alternative route for glutamate production in glial cells of the hippocampus [87].…”

Section: Testing the Hypothesismentioning

confidence: 99%

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

2002

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Abstract

Background

A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors.

Presentation of the hypothesis

Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells). This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia.

Testing the hypothesis

Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations.

Implications of the hypothesis

The hypothesis suggests glial cells as the locus of the genes-environment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments.

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“…Several studies have demonstrated the presence of a serotonergic mechanism in the LPBN that modulates sodium and water intake (Colombari et al, 1996; De Gobbi et al, 2000; De Gobbi et al, 2001; Menani et al, 1996; Menani et al, 1998; Menani et al, 2000; Menani et al, 2002; Menani and Johnson, 1995). In general, the localization of serotonin (5-HT) at a site in the brain is accompanied by the presence of glutamate (Maione et al, 1997; Meller et al, 2002; Scruggs et al, 2000; Singewald et al, 1998). Glutamate has been identified by immunocytochemistry to be present in the parabrachial nucleus (PBN) (Gill et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Non-NMDA receptors in the lateral parabrachial nucleus modulate sodium appetite

et al. 2009

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Glutamatergic mechanisms have been implicated in the control of fluid ingestion. In the present study, we investigated whether non-N-methyl-D-aspartate (NMDA) glutamatergic receptors in the lateral parabrachial nucleus (LPBN) are involved in the control of water and sodium intake. Male Sprague-Dawley rats had cannulas implanted bilaterally into the LPBN. They were acutely depleted of water and sodium by injections of the diuretic furosemide (Furo; 10 mg/kg, bw) and given a low dose of the angiotensin-converting enzyme inhibitor, captopril (Cap; 5 mg/kg, bw). Bilateral LPBN injections of the non-NMDA receptor antagonist DNQX (2 and 5 nmol/0.2 µl) increased the ingestion of 0.3 M NaCl and water of Furo/Cap treated rats. The increased ingestion produced by DNQX was abolished by pretreating the LPBN with α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), a non-NMDA receptor agonist. AMPA injected alone into the LPBN reduced water and 0.3 M NaCl intake. Injections of DNQX (5 nmol/0.2 µl) into the LPBN also produced ingestion of 0.3 M NaCl after sc injections of the β-adrenoceptor agonist, isoproterenol, a hypotensive drug that typically produces only water intake. Food intake, arterial blood pressure and heart rate were not altered by DNQX LPBN injections. We conclude that agonists acting on non-NMDA receptors in the LPBN exert an inhibitory influence on sodium intake during acute fluid depletion with hypotension and after isoproterenol treatment. A possible interaction of serotonin with glutamate within the LPBN is discussed. Keywordsglutamate; α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA); fluid and electrolyte balance; sodium appetite/intake; thirst

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In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT_2A receptor activation

Cited by 38 publications

References 36 publications

Role of 5-HT1A receptors in the modulation of stress-induced lactate metabolism in the medial prefrontal cortex and basolateral amygdala

Role of 5-HT1A receptors in the modulation of stress-induced lactate metabolism in the medial prefrontal cortex and basolateral amygdala

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

Non-NMDA receptors in the lateral parabrachial nucleus modulate sodium appetite

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In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT2A receptor activation

Cited by 38 publications

References 36 publications

Role of 5-HT1A receptors in the modulation of stress-induced lactate metabolism in the medial prefrontal cortex and basolateral amygdala

Role of 5-HT1A receptors in the modulation of stress-induced lactate metabolism in the medial prefrontal cortex and basolateral amygdala

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

Non-NMDA receptors in the lateral parabrachial nucleus modulate sodium appetite

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In vitro evidence that 5‐hydroxytryptamine increases efflux of glial glutamate via 5‐HT_2A receptor activation