CSF monoamine metabolites in dementia of the Alzheimer type and controls: Evidence for lower levels of homovanillic acid and 5‐hydroxyindoleacetic acid in patients

Westenberg, H.G.M.; Verhoeven, W.M.A.

doi:10.1002/gps.930030408

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…Inter-assay variation was between 3.8 % and 4.6 % and detection limit was 0.01 µmol / l. Plasma HVA was determined by HPLC in conjunction with an electrochemical detector. After precipitation of protein with trichloroacetic acid and neutralization with sodium bicarbonate, an aliquot of the supernatant was assayed as described previously (Westenberg and Verhoeven 1988).…”

Section: P50 Taskmentioning

confidence: 99%

The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects

et al. 1998

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Recently, much interest has been given to the role of glutamatergic N-methyl-D-aspartate receptors (NMDA) in sensory gating, such as prepulse inhibition (PPI) and reduction of the P50 evoked response potential (ERP). Currently, mainly animal data are available describing the role of NMDA receptors in these stimulus evaluation processes. Human data are virtually lacking and are potentially important, for instance for the understanding of sensory gating deficits observed in schizophrenia. Therefore, the effects of the NMDA antagonist ketamine, in a dose of 0.3 mg/kg i.v., on concurrent assessment of PPI and P50 reduction was studied in 18 healthy male volunteers. Ketamine was administered in a pseudo-steady state model with a subacute loading dose. In addition, the effects of ketamine on behavior, vital signs, homovanillic acid (HVA) plasma levels and secretion of cortisol and luteinizing hormone (LH) were also determined. Ketamine did not significantly alter PPI or the reduction of the P50 ERP. A small but significant increase in Brief Psychiatric Rating Scale (BPRS) total scores and BPRS composite scores "thinking disorder" and "withdrawal/retardation" was observed. Several subjects experienced visual perceptional alterations, but complex hallucinations did not occur. Ketamine induced mild analgesia and coordination problems. In addition, ketamine induced a marked rise in cortisol secretion, while LH secretion was not affected. Finally, systolic and diastolic, blood pressure and heart rate increased during ketamine infusion. Although in humans NMDA receptors may not be involved in the regulation of PPI and P50 reduction, the most likely explanation for the lack of effect of ketamine on these sensory gating paradigms is the dose used in this experiment. However, using a higher dose is hampered by the aspecificity of racemic ketamine. Future studies should use the enantiomer S-ketamine, which is more specific to NMDA receptors, to evaluate the involvement of NMDA receptors in these neurophysiological processes further.

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Section: P50 Taskmentioning

confidence: 99%

The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects

et al. 1998

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“…After precipitation of protein with trichloroacetic acid and neutralization with sodium bicarbonate, an aliquot of the supernatant was assayed as described previously (Westenberg and Verhoeven 1988). After precipitation of protein with trichloroacetic acid and neutralization with sodium bicarbonate, an aliquot of the supernatant was assayed as described previously (Westenberg and Verhoeven 1988).…”

Section: Assessment Of Plasma Hva Levelsmentioning

confidence: 99%

The partial NMDA agonist D -cycloserine stimulates LH secretion in healthy volunteers

et al. 1998

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D-Cycloserine, a partial agonist of the glycine recognition site of the N-methyl-D-aspartate (NMDA) receptor, may serve as a probe for human cerebral NMDA receptor function. Since NMDA receptors are involved in neuroendocrine secretion, changes in pituitary secretion in response to D-cycloserine administration could serve as a model for NMDA receptor activity. The effects of an oral dose of 500 mg D-cycloserine were assessed in a neuroendocrine challenge paradigm in 20 healthy male volunteers, using a double-blind, randomized placebo-controlled crossover design. Luteinizing hormone (LH) and cortisol secretion was studied, since preclinical studies indicate that these hormones increase in response to NMDA receptor stimulation. Furthermore, plasma homovanillic acid (HVA) secretion was studied, as NMDA receptors are suggested to be involved in the regulation of dopaminergic neurotransmission. D-cycloserine was readily absorbed and did not induce side-effects or changes in vital signs and mood scores. D-Cycloserine stimulated LH secretion and induced a significant rise of the area under the plasma concentration time curve of LH. D-Cycloserine did not stimulate cortisol or plasma HVA secretion. These neuroendocrine effects suggest that D-cycloserine may be used to assess human NMDA receptor function in cerebral disorders, such as schizophrenia.

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“…17 In een recent onderzoek van Westenberg en Verhoeven werd bij 15 patienten (zeven vrouwen en acht mannen) in de leeftijd van 49 tot 72 jaar de concentratie van HVZ en 5-HIAZ bepaald en vergeleken met een voor leeftijd en geslacht gecorrigeerde controlegroep van 48 personen (21 mannen en 27 vrouwen; leeftijd 22 tot 74 jaar). 8 Bij de patienten werd een significante verlaging gevonden van zowel de 5-HIAZ als de HVZ concentratie. Opmerkelijk was echter de bevinding dat deze verlaging het meest uitgesproken was bij de mannelijke patienten, hetgeen zou kunnen betekenen dat geslachtsgebonden factoren betrokken zijn bij de ontwikkeling van het degeneratieve proces.…”

Section: Dementieen Van Het Type Alzheimerunclassified

Monoamines and CSF: relevance to neuropsychiatric disorders

Verhoeven¹

1992

Acta Neuropsychiatr.

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Over the past 25 years much effort has been put into the research of the relationship between neuropsychiatric disorders and the concentrations of CSF-monoamine metabolites. Most of this research has beenfocused on the relation between CSF-concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and specific symptomatological entities, particularly schizophrenia, Alzheimer's dementia and endogenous depression. It appeared that specific relations between diseases and CSF-concentrations of monoamine metabolites cannot be longer maintained and that a more functional psychopathology should be considered as the future research strategy.

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CSF monoamine metabolites in dementia of the Alzheimer type and controls: Evidence for lower levels of homovanillic acid and 5‐hydroxyindoleacetic acid in patients

Cited by 4 publications

References 33 publications

The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects

The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects

The partial NMDA agonist D -cycloserine stimulates LH secretion in healthy volunteers

Monoamines and CSF: relevance to neuropsychiatric disorders

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