Relationships between glutamate and monoamine metabolites in cerebrospinal fluid and serum in healthy volunteers

Alfredsson, Gunnel; Wiesel, Frits‐Axel; Tylec, A.

doi:10.1016/0006-3223(88)90052-2

Cited by 70 publications

(48 citation statements)

References 26 publications

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“…This is consistent with several studies reporting diminished glutamate function in schizophrenics, including a decrease in CSF levels of glutamate (Kim et al, 1980; but see Perry, 1982), an increase in glutamate binding in the striatum (Kornhuber et al, 1989), increased kainate binding in the frontal cortex (presumably to presynaptic autoreceptors on glutamatergic terminals; Nishikawa et al, 1983a;Deakin et al, 1989), and a diminished efflux of glutamate from synaptosomes derived from schizophrenic brains (Sherman et al, 1991). A decrease in glutamate release in the ventral striatum should, in turn, decrease glutamate-stimulated tonic DA release, which is consistent with the reported negative correlation between glutamate levels and HV A concentration in the CSF of schizophrenics (Alfredsson et al, 1988).…”

Section: Systems Involved In the Induction Of Depolarization Blocksupporting

confidence: 76%

The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia

Grace

1992

Advances in Neuroscience and Schizophrenia

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Summary. Antipsychotic drugs are known to block dopamine receptors soon after their administration, resulting in an increase in dopamine neuron firing and dopamine turnover. Nonetheless, antipsychotic drugs must be administered repeatedly to schizophrenics before therapeutic benefits are produced. Recordings from dopamine neurons in rats have revealed that chronic antipsychotic drug treatment results in the time-dependent inactivation of dopamine neuron firing via over-excitation, or depolarization block. Furthermore, the clinical profile of the response to antipsychotic drugs appears to correspond to the dopamine system affected: antipsychotic drugs that exert therapeutic actions in schizophrenics inactivate dopamine neuron firing in the limbic-related ventral tegmental area, whereas drugs that precipitate extrapyramidal side effects cause depolarization block of the motor-related substantia nigra dopamine cells.One factor that remains unresolved with regard to the actions of antipsychotic drugs is the relationship between dopamine turnover and depolarization block -i.e., why does a significant level of dopamine release or turnover remain after antipsychotic drug treatment if dopamine cells are no longer firing? We addressed this question using an acute model of neuroleptic-induced depolarization block. In this model, dopamine cells recorded in rats one month after partial dopamine lesions could be driven into depolarization block by the acute administration of moderate doses of haloperidol. However, similar doses of haloperidol, which were effective at increasing dopamine levels in the striatum of intact rats, failed to change dopamine levels in lesioned rats. This is consistent with a model in which neuroleptic drugs exert their therapeutic effects in schizophrenics by causing depolarization block in DA cells, thereby preventing further activation of dopamine neuron firing in response to external stimuli. Thus, attenuating the responsivity of the dopamine system to stimuli may be more relevant to the therapeutic actions of antipsychotic drugs than receptor blockade or decreases in absolute levels of dopamine, which could presumably be circumvented by homeostatic adaptations in this highly plastic system.

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Section: Systems Involved In the Induction Of Depolarization Blocksupporting

confidence: 76%

The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia

Grace

1992

Advances in Neuroscience and Schizophrenia

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“…Therefore, controversies prevail whether to consider autism as a hyperglutamatergic or a hypoglutamatergic disorder. Although glutamate is considered not to readily cross the blood-brain barrier, the level of glutamate in the blood is correlated positively with the cerebrospinal fluid level of glutamate in humans [11]. Therefore, the aim of this study was to investigate the plasma circulating levels of glutamate in Chinese children with ASD by comparing them with age-matched and sex-matched healthy and intellectual disability (ID) controls.…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma levels of glutamate in children with autism spectrum disorders

et al. 2016

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Excitatory neurotransmitter signaling through glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in autism spectrum disorders (ASD). The aim of this study was to assess the clinical significance of plasma glutamate levels in ASD. Fifty-one children diagnosed with ASD, 51 typically developing children, and 51 children with intellectual disability matched for sex and age were assessed for plasma glutamate at admission. Plasma levels of glutamate were measured by liquid chromatography-tandem mass spectrometry and the severity of ASD was evaluated using the Childhood Autism Rating Scale Score. We found that the mean plasma glutamate levels were significantly (P<0.0001) higher in children with ASD compared with healthy controls and intellectual disability controls [36.1 (SD: 8.3) vs. 23.4 (4.2) vs. 24.7 (4.6) µM; P<0.001, respectively]. Levels of glutamate increased with increasing severity of ASD as defined by the Childhood Autism Rating Scale score. Receiver operating characteristics to diagnose ASD showed areas under the curve of glutamate of 0.92 [95% confidence interval (CI), 0.87-0.96], which was superior to high-sensitivity C-reactive protein [0.64 (95% CI, 0.55-0.75), P<0.001] and homocysteine (area under the curve, 0.72; 95% CI, 0.64-0.81; P<0.000). In multivariate logistic regression analysis, glutamate was an independent diagnosis indicator of ASD with an adjusted odds ratio of 1.362 (95% CI, 1.164-1.512; P<0.0001). The present study shows that autistic children had higher plasma levels of glutamate and elevated plasma glutamate levels may play an important role in the pathogenesis of autism. Further larger studies are required to support our findings.

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“…In substance addiction, drugs of abuse alter glutamate transmission29); nicotine enhances extracellular levels of glutamate,30) opiate reduces synaptic overflow of glutamate,31) and alcohol has mixed effect on extracellular levels of glutamate 11). In addition to these direct effects, glutamate regulates dopaminergic activity and thus modulates dopaminergic reward processing via incentive arousal for drug-related cue 23,32). Conditioned drug-related cue elicits a phasic increase in the firing of ventral tegmental area dopamine neuron and eventually lead to the co-release of dopamine and glutamate in prefrontal cortex and the nucleus accumbens 22).…”

Section: Discussionmentioning

confidence: 99%

“…Since serum levels of glutamate are positively correlated with the cerebrospinal fluid levels of glutamate in humans,23) altered glutamate neurotransmission in the brain can be inferred from the changes in the serum levels of glutamate. Thus the present pilot study assessed the serum levels of glutamate and dopamine in male adults with IGD without psychiatric comorbidities in comparison with healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Decreased Serum Glutamate Levels in Male Adults with Internet Gaming Disorder: A Pilot Study

Paik

Choi

Kwak

et al. 2018

Clin Psychopharmacol Neurosci

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ObjectiveAlteration in glutamatergic neurotransmission and dopaminergic dysfunction has been implicated in both the initiation and expression of addiction related behaviors. This pilot study was aimed to investigate the serum levels of glutamate and dopamine in adults with internet gaming disorder (IGD).MethodsWe measured serum levels of glutamate and dopamine in male participants with IGD (n=26) and age-matched healthy controls (n=25). Clinical interviews were performed to identify IGD and to rule out psychiatric comorbidities. Serum levels of glutamate and dopamine were examined by enzyme immunoassays using ELISA Kits.ResultsSerum levels of glutamate were lower among IGD than control (IGD: 24.184±12.303 μg/ml; control: 33.676±12.413μg/ml; t=2.742, p=0.008), while levels of dopamine did not differ between. Serum glutamate and dopamine levels did not correlate with gaming hours and exposure to game in the IGD group. But serum glutamate levels were positively correlated with the dopamine levels (r=0.360, p=0.013).ConclusionOur results suggest that altered glutamatergic neurotransmission may contribute to the pathophysiology of IGD.

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Relationships between glutamate and monoamine metabolites in cerebrospinal fluid and serum in healthy volunteers

Cited by 70 publications

References 26 publications

The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia

The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia

Elevated plasma levels of glutamate in children with autism spectrum disorders

Decreased Serum Glutamate Levels in Male Adults with Internet Gaming Disorder: A Pilot Study

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