Review: Glutamate and dopamine dysregulation in schizophrenia — a                 synthesis and selective review

Stone, James; Morrison, Paul; Pilowsky, Lyn S.

doi:10.1177/0269881106073126

Cited by 333 publications

(233 citation statements)

References 149 publications

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“…Chronic NMDAR antagonism led to a marked increase of intracellular glutamate in the hippocampus. In addition, current proponents of the glutamatergic hypothesis postulate that hypofunctional NMDAR located on gamma-aminobutyric acid (GABA)-ergic inhibitory interneurons disinhibit pyramidal neurons, leading to a paradoxical increase of glutamatergic activity within the prefrontal cortex and striatum, promoting the development of positive and negative symptoms (Stone et al 2007, Nakazawa et al 2012). An important neuromodulatory role of AA appears to involve the presynaptic re-uptake of glutamate.…”

Section: Discussionmentioning

confidence: 99%

The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine

Damázio

Silveira

Canever

et al. 2017

An. Acad. Bras. Ciênc.

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Studies have shown that schizophrenic patients seem to have nutritional deficiencies. Ascorbic acid (AA) has an important antioxidant effect and neuromodulatory properties. The aim of this study was to evaluate the effects of AA on locomotor activity and the acetylcholinesterase activity (AChE) in an animal model of schizophrenia (SZ). Rats were supplemented with AA (0.1, 1, or 10 mg/kg), or water for 14 days (gavage). Between the 9th and 15th days, the animals received Ketamine (Ket) (25 mg/kg) or saline (i.p). After the last administration (30 min) rats were subjected to the behavioral test. Brain structures were dissected for biochemical analysis. There was a significant increase in the locomotor activity in Ket treated. AA prevented the hyperlocomotion induced by ket. Ket also showed an increase of AChE activity within the prefrontal cortex and striatum prevented by AA. Our data indicates an effect for AA in preventing alterations induced by Ket in an animal model of SZ, suggesting that it may be an adjuvant approach for the development of new therapeutic strategies within this psychiatric disorder.

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Section: Discussionmentioning

confidence: 99%

The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine

Damázio

Silveira

Canever

et al. 2017

An. Acad. Bras. Ciênc.

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“…This was associated with increased 3 H-Haloperidol binding in the striatum, as found in studies of male rats following maternal malnutrition 121,149 , although there are conflicting reports of this 150 . Increased 3 H-MK-801 binding in the striatum and hippocampus was described in the maternal malnutrition model and may reflect a NMDA receptor hypofunction and subsequent up-regulation as postulated by the glutamate hypothesis of schizophrenia 121,151 . Memory deficits in this model were described in terms of susceptibility to interference and extinction, further supporting theories of prefrontal and hippocampal psychopathology 152 .…”

Section: Maternal Protein Malnutritionmentioning

confidence: 93%

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Gottschalk

Sarnyai

Guest

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Psychiatric symptoms are subjective by nature and tend to overlap between different disorders. The modelling of a neuropsychiatric disorder therefore faces challenges because of missing knowledge of the fundamental pathophysiology and a lack of accurate diagnostics. Animal models are used to test hypotheses of aetiology and to represent the human condition as close as possible to increase our understanding of the disease and to evaluate new targets for drug discovery. In this review, genetic and neurodevelopmental animal models of schizophrenia are discussed with respect to behavioural and neurophysiological findings and their association with the clinical condition. Only specific animal models of schizophrenia may ultimately lead to novel diagnostic approaches and drug discovery. We argue that molecular biomarkers are important to improve animal to human translation since behavioural readouts lack the necessary specificity and reliability to assess human psychiatric symptoms.Gottschalk MG, et al. / Rev Psiq Clín. 2013;40(1):41-50 Keywords: Translational research, neuropsychiatry, genetic, neurodevelopment, animal model, schizophrenia. ResumoSintomas psiquiátricos são subjetivos por natureza e tendem a se sobrepor entre diferentes desordens. Sendo assim, a criação de modelos de uma desordem neuropsiquiátrica encontra desafios pela falta de conhecimento dos fundamentos da fisiopatologia e diagnósticos precisos. Modelos animais são usados para testar hipóteses de etiologia e para representar a condição humana tão próximo quanto possível para aumentar nosso entendimento da doença e avaliar novos alvos para a descoberta de drogas. Nesta revisão, modelos animais genéticos e de neurodesenvolvimento de esquizofrenia são discutidos com respeito a achados comportamentais e neurofisiológicos e sua associação com a condição clínica. Somente modelos animais específicos de esquizofrenia podem, em último caso, levar a novas abordagens diagnósticas e descoberta de drogas. Argumentamos que biomarcadores moleculares são importantes para aumentar a tradução de animais a humanos, já que faltam a especificidade e a fidelidade necessárias às leituras comportamentais para avaliar sintomas psiquiátricos humanos.Gottschalk MG, et al. / Rev Psiq Clín. 2013;40(1):41-50

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“…Both clozapine and olanzapine elevate cortical dopamine and norepinephrine outflow to a greater extent than FGAs such as haloperidol (Devoto and Flore, 2006;Li et al, 1998;Moghaddam and Bunney, 1990;Nomikos et al, 1994;Westerink et al, 1998). In contrast to FGAs, both clozapine and olanzapine also markedly facilitate cortical NMDA receptor-mediated transmission (Jardemark et al, 2002;, an effect that may contribute to improve negative symptoms and cognitive dysfunction in schizophrenia (see eg Stone et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Reboxetine Enhances the Olanzapine-Induced Antipsychotic-Like Effect, Cortical Dopamine Outflow and NMDA Receptor-Mediated Transmission

Marcus¹,

Jardemark²,

Malmerfelt³

et al. 2010

Neuropsychopharmacol

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Preclinical data have shown that addition of the selective norepinephrine transporter (NET) inhibitor reboxetine increases the antipsychotic-like effect of the D 2/3 antagonist raclopride and, in parallel, enhances cortical dopamine output. Subsequent clinical results suggested that adding reboxetine to stable treatments with various antipsychotic drugs (APDs) may improve positive, negative and depressive symptoms in schizophrenia. In this study, we investigated in rats the effects of adding reboxetine to the second-generation APD olanzapine on: (i) antipsychotic efficacy, using the conditioned avoidance response (CAR) test, (ii) extrapyramidal side effect (EPS) liability, using a catalepsy test, (iii) dopamine efflux in the medial prefrontal cortex and the nucleus accumbens, using in vivo microdialysis in freely moving animals and (iv) cortical N-methyl-D-aspartate (NMDA) receptor-mediated transmission, using intracellular electrophysiological recording in vitro. Reboxetine (6 mg/kg) enhanced the suppression of CAR induced by a suboptimal dose (1.25 mg/kg), but not an optimal (2.5 mg/kg) dose of olanzapine without any concomitant catalepsy. Addition of reboxetine to the low dose of olanzapine also markedly increased cortical dopamine outflow and facilitated prefrontal NMDA receptor-mediated transmission. Our data suggest that adjunctive treatment with a NET inhibitor may enhance the therapeutic effect of low-dose olanzapine in schizophrenia without increasing EPS liability and add an antidepressant action, thus in principle allowing for a dose reduction of olanzapine with a concomitant reduction of dose-related side effects, such as EPS and weight gain.

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Review: Glutamate and dopamine dysregulation in schizophrenia — a synthesis and selective review

Cited by 333 publications

References 149 publications

The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine

The preventive effects of ascorbic acid supplementation on locomotor and acetylcholinesterase activity in an animal model of schizophrenia induced by ketamine

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Reboxetine Enhances the Olanzapine-Induced Antipsychotic-Like Effect, Cortical Dopamine Outflow and NMDA Receptor-Mediated Transmission

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