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Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude.
Int J Neuropsychopharmacol 2009; 12(6):823-32IJ

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.

Authors+Show Affiliations

Center for Neuropsychiatric Schizophrenia Research (CNSR), Faculty of Health Sciences, Copenhagen University, University Psychiatric Center Glostrup, Glostrup, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

19154656

Citation

Oranje, Bob, et al. "Haloperidol Counteracts the Ketamine-induced Disruption of Processing Negativity, but Not That of the P300 Amplitude." The International Journal of Neuropsychopharmacology, vol. 12, no. 6, 2009, pp. 823-32.
Oranje B, Gispen-de Wied CC, Westenberg HG, et al. Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude. Int J Neuropsychopharmacol. 2009;12(6):823-32.
Oranje, B., Gispen-de Wied, C. C., Westenberg, H. G., Kemner, C., Verbaten, M. N., & Kahn, R. S. (2009). Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude. The International Journal of Neuropsychopharmacology, 12(6), pp. 823-32. doi:10.1017/S1461145708009814.
Oranje B, et al. Haloperidol Counteracts the Ketamine-induced Disruption of Processing Negativity, but Not That of the P300 Amplitude. Int J Neuropsychopharmacol. 2009;12(6):823-32. PubMed PMID: 19154656.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2009/01/21/ PY - 2009/1/22/entrez PY - 2009/1/22/pubmed PY - 2009/8/19/medline SP - 823 EP - 32 JF - The international journal of neuropsychopharmacology JO - Int. J. Neuropsychopharmacol. VL - 12 IS - 6 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. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/19154656/Haloperidol_counteracts_the_ketamine_induced_disruption_of_processing_negativity_but_not_that_of_the_P300_amplitude_ L2 - https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145708009814 DB - PRIME DP - Unbound Medicine ER -