Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude

Bob Oranje; Christine C Gispen-de Wied; Herman G M Westenberg; Chantal Kemner; Marinus N Verbaten; René S Kahn

doi:10.1017/S1461145708009814

Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude

Bob Oranje, Christine C Gispen-de Wied, Herman G M Westenberg, Chantal Kemner, Marinus N Verbaten, René S Kahn

Department of Clinical Medicine

13 Citations (Scopus)

Abstract

Antagonists of the N-methyl-D-aspartate (NMDA) receptors such as ketamine, induce abnormalities in healthy subjects similar to those found in schizophrenia. However, recent evidence, suggests that most of the currently known NMDA antagonists have a broader receptor profile than originally thought. Besides exerting an antagonistic effect on NMDA receptors, they have agonistic effects on dopamine D2 receptors. Can haloperidol (D2 antagonist) counteract the disruptive effects of ketamine on psychophysiological parameters of human attention? In a randomized, double-blind, placebo-controlled experiment 18 healthy male volunteers received placebo/placebo, placebo/ketamine (0.3 mg/kg i.v.) and haloperidol (2 mg)/ketamine (0.3 mg/kg i.v.) on three separate test days, after which they were tested in an auditory selective-attention paradigm. Haloperidol/ketamine reduced task performance compared to placebo/placebo, while the task performance in these two treatments did not differ from placebo/ketamine. Furthermore, placebo/ketamine reduced processing negativity compared to both placebo/placebo and haloperidol/ketamine, while processing negativity did not differ between placebo/placebo and haloperidol/ketamine treatments. However, both placebo/ketamine and haloperidol/ketamine reduced P300 amplitude compared to placebo/placebo, while P300 amplitude did not differ between placebo/ketamine and haloperidol/ketamine treatments. The combined effects of haloperidol and ketamine reduced task performance, suggesting that this is dependent on dopaminergic D2 activity, probably in the prefrontal cortex. In addition, ketamine reduced both P300 amplitude and processing negativity. In contrast to the P300 amplitude, the disruptive effects of ketamine on processing negativity could be prevented by pretreatment with haloperidol. The current results suggest that ketamine reduced P300 amplitude by its antagonistic effect on glutamatergic activity, while it reduced processing negativity by its agonistic effect on dopaminergic D2 activity.

Original language	English
Journal	International Journal of Neuropsychopharmacology
Volume	12
Issue number	6
Pages (from-to)	823-32
Number of pages	9
ISSN	1461-1457
DOIs	https://doi.org/10.1017/S1461145708009814
Publication status	Published - 2009

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1017/S1461145708009814

Cite this

@article{2d4fa320a6a611df928f000ea68e967b,

title = "Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude",

abstract = "Antagonists of the N-methyl-D-aspartate (NMDA) receptors such as ketamine, induce abnormalities in healthy subjects similar to those found in schizophrenia. However, recent evidence, suggests that most of the currently known NMDA antagonists have a broader receptor profile than originally thought. Besides exerting an antagonistic effect on NMDA receptors, they have agonistic effects on dopamine D2 receptors. Can haloperidol (D2 antagonist) counteract the disruptive effects of ketamine on psychophysiological parameters of human attention? In a randomized, double-blind, placebo-controlled experiment 18 healthy male volunteers received placebo/placebo, placebo/ketamine (0.3 mg/kg i.v.) and haloperidol (2 mg)/ketamine (0.3 mg/kg i.v.) on three separate test days, after which they were tested in an auditory selective-attention paradigm. Haloperidol/ketamine reduced task performance compared to placebo/placebo, while the task performance in these two treatments did not differ from placebo/ketamine. Furthermore, placebo/ketamine reduced processing negativity compared to both placebo/placebo and haloperidol/ketamine, while processing negativity did not differ between placebo/placebo and haloperidol/ketamine treatments. However, both placebo/ketamine and haloperidol/ketamine reduced P300 amplitude compared to placebo/placebo, while P300 amplitude did not differ between placebo/ketamine and haloperidol/ketamine treatments. The combined effects of haloperidol and ketamine reduced task performance, suggesting that this is dependent on dopaminergic D2 activity, probably in the prefrontal cortex. In addition, ketamine reduced both P300 amplitude and processing negativity. In contrast to the P300 amplitude, the disruptive effects of ketamine on processing negativity could be prevented by pretreatment with haloperidol. The current results suggest that ketamine reduced P300 amplitude by its antagonistic effect on glutamatergic activity, while it reduced processing negativity by its agonistic effect on dopaminergic D2 activity.",

author = "Bob Oranje and {Gispen-de Wied}, {Christine C} and Westenberg, {Herman G M} and Chantal Kemner and Verbaten, {Marinus N} and Kahn, {Ren{\'e} S}",

note = "Keywords: Acoustic Stimulation; Adult; Affect; Attention; Behavior; Blood Pressure; Contingent Negative Variation; Dopamine Antagonists; Double-Blind Method; Drug Interactions; Electroencephalography; Electrooculography; Event-Related Potentials, P300; Excitatory Amino Acid Antagonists; Haloperidol; Heart Rate; Homovanillic Acid; Humans; Ketamine; Male; Multivariate Analysis; Neuropsychological Tests; Prolactin; Psychiatric Status Rating Scales; Reaction Time; Time Factors; Young Adult",

year = "2009",

doi = "10.1017/S1461145708009814",

language = "English",

volume = "12",

pages = "823--32",

journal = "International Journal of Neuropsychopharmacology",

issn = "1461-1457",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude

AU - Oranje, Bob

AU - Gispen-de Wied, Christine C

AU - Westenberg, Herman G M

AU - Kemner, Chantal

AU - Verbaten, Marinus N

AU - Kahn, René S

N1 - Keywords: Acoustic Stimulation; Adult; Affect; Attention; Behavior; Blood Pressure; Contingent Negative Variation; Dopamine Antagonists; Double-Blind Method; Drug Interactions; Electroencephalography; Electrooculography; Event-Related Potentials, P300; Excitatory Amino Acid Antagonists; Haloperidol; Heart Rate; Homovanillic Acid; Humans; Ketamine; Male; Multivariate Analysis; Neuropsychological Tests; Prolactin; Psychiatric Status Rating Scales; Reaction Time; Time Factors; Young Adult

PY - 2009

Y1 - 2009

N2 - Antagonists of the N-methyl-D-aspartate (NMDA) receptors such as ketamine, induce abnormalities in healthy subjects similar to those found in schizophrenia. However, recent evidence, suggests that most of the currently known NMDA antagonists have a broader receptor profile than originally thought. Besides exerting an antagonistic effect on NMDA receptors, they have agonistic effects on dopamine D2 receptors. Can haloperidol (D2 antagonist) counteract the disruptive effects of ketamine on psychophysiological parameters of human attention? In a randomized, double-blind, placebo-controlled experiment 18 healthy male volunteers received placebo/placebo, placebo/ketamine (0.3 mg/kg i.v.) and haloperidol (2 mg)/ketamine (0.3 mg/kg i.v.) on three separate test days, after which they were tested in an auditory selective-attention paradigm. Haloperidol/ketamine reduced task performance compared to placebo/placebo, while the task performance in these two treatments did not differ from placebo/ketamine. Furthermore, placebo/ketamine reduced processing negativity compared to both placebo/placebo and haloperidol/ketamine, while processing negativity did not differ between placebo/placebo and haloperidol/ketamine treatments. However, both placebo/ketamine and haloperidol/ketamine reduced P300 amplitude compared to placebo/placebo, while P300 amplitude did not differ between placebo/ketamine and haloperidol/ketamine treatments. The combined effects of haloperidol and ketamine reduced task performance, suggesting that this is dependent on dopaminergic D2 activity, probably in the prefrontal cortex. In addition, ketamine reduced both P300 amplitude and processing negativity. In contrast to the P300 amplitude, the disruptive effects of ketamine on processing negativity could be prevented by pretreatment with haloperidol. The current results suggest that ketamine reduced P300 amplitude by its antagonistic effect on glutamatergic activity, while it reduced processing negativity by its agonistic effect on dopaminergic D2 activity.

AB - Antagonists of the N-methyl-D-aspartate (NMDA) receptors such as ketamine, induce abnormalities in healthy subjects similar to those found in schizophrenia. However, recent evidence, suggests that most of the currently known NMDA antagonists have a broader receptor profile than originally thought. Besides exerting an antagonistic effect on NMDA receptors, they have agonistic effects on dopamine D2 receptors. Can haloperidol (D2 antagonist) counteract the disruptive effects of ketamine on psychophysiological parameters of human attention? In a randomized, double-blind, placebo-controlled experiment 18 healthy male volunteers received placebo/placebo, placebo/ketamine (0.3 mg/kg i.v.) and haloperidol (2 mg)/ketamine (0.3 mg/kg i.v.) on three separate test days, after which they were tested in an auditory selective-attention paradigm. Haloperidol/ketamine reduced task performance compared to placebo/placebo, while the task performance in these two treatments did not differ from placebo/ketamine. Furthermore, placebo/ketamine reduced processing negativity compared to both placebo/placebo and haloperidol/ketamine, while processing negativity did not differ between placebo/placebo and haloperidol/ketamine treatments. However, both placebo/ketamine and haloperidol/ketamine reduced P300 amplitude compared to placebo/placebo, while P300 amplitude did not differ between placebo/ketamine and haloperidol/ketamine treatments. The combined effects of haloperidol and ketamine reduced task performance, suggesting that this is dependent on dopaminergic D2 activity, probably in the prefrontal cortex. In addition, ketamine reduced both P300 amplitude and processing negativity. In contrast to the P300 amplitude, the disruptive effects of ketamine on processing negativity could be prevented by pretreatment with haloperidol. The current results suggest that ketamine reduced P300 amplitude by its antagonistic effect on glutamatergic activity, while it reduced processing negativity by its agonistic effect on dopaminergic D2 activity.

U2 - 10.1017/S1461145708009814

DO - 10.1017/S1461145708009814

M3 - Journal article

C2 - 19154656

SN - 1461-1457

VL - 12

SP - 823

EP - 832

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

IS - 6

ER -

Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this