No effects of l-dopa and bromocriptine on psychophysiological parameters of human selective attention

Oranje, Bob; Wied, Christine C. Gispen‐de; Westenberg, H. G. M.; Kemner, Chantal; Verbaten, Marinus N.; Kahn, René S.

doi:10.1177/0269881106061712

Cited by 20 publications

(12 citation statements)

References 51 publications

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“…However, the combination of pretreatment with haloperidol and subsequent ketamine administration resulted in a significantly decreased number of hits, which suggests that haloperidol is responsible for this effect. The concept that P300 amplitude is not modulated by dopaminergic activity is consistent with earlier results from our laboratory, in which neither an effect of bromocriptine (selective D 2 agonist) nor of L-dopa (precursor of dopamine) was found on P300 amplitude of healthy volunteers (Oranje et al 2006). Haloperidol reduces metabolism in the frontal cortex (Holcomb et al 1996 ;Wolkin et al 1996), the cerebrum (Wolkin et al 1996) and throughout the entire central nervous system (Bartlett et al 1998).…”

Section: Discussionsupporting

confidence: 91%

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

Oranje

Wied

Westenberg

et al. 2009

Int. J. Neuropsychopharm.

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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.

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Section: Discussionsupporting

confidence: 91%

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

Oranje

Wied

Westenberg

et al. 2009

Int. J. Neuropsychopharm.

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“…While in vitro , ketamine has affinity not only for NMDA but several other receptors including dopamine (58), selective D 2 agonist bromocriptine, dopamine precursor L-dopa (59) and D 1 and D 2 agonist apomorphine did not affect P300 amplitude in healthy volunteers (60). Consistent with these findings, pretreatment with the D 2 antagonist haloperidol did not affect ketamine’s effect on P300 (61).…”

Section: Discussionmentioning

confidence: 99%

Glutamatergic Modulation of Auditory Information Processing in the Human Brain

Gunduz‐Bruce

Reinhart

Roach

et al. 2012

Biological Psychiatry

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Background Auditory mismatch negativity (MMN) and P300 event related potentials (ERP) are reduced in schizophrenia patients, and healthy volunteers administered the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, ketamine. In rodents, N-acetylcysteine (NAC), a stimulator of the cystine-glutamate exchanger, attenuates the cognitive and behavioral effects of NMDA receptor antagonists. Based on these findings, we tested whether NAC would reduce ketamine effects on behavior, MMN, and P300 in healthy humans. Methods This randomized, double-blind, placebo-controlled study consisted of two test days during which subjects (N=16) were administered oral NAC (3000 mg in divided doses) or matching placebo 165 minutes prior to the infusion of saline and then ketamine (as a bolus of 0.23 mg/kg over one minute followed by 0.58 mg/kg for 30 min, and then 0.29 mg/kg for 40 min) in a fixed order. Behavioral and ERP data including auditory MMN and P300 were collected during each test day. Results Ketamine produced psychotic-like positive symptoms, reductions in working memory and sustained attention performance, and amplitude reductions for the frequency- and intensity-deviant MMNs and P300. NAC pretreatment did not reduce the behavioral or ERP effects of ketamine. In addition, NAC reduced frequency-deviant MMN amplitude and increased target and novelty P3 amplitudes. The decrements in frequency-deviant MMN amplitude produced by ketamine and NAC were not additive. Conclusions In contrast to previous studies in animals, NAC did not attenuate the effects of ketamine in humans. NAC merits further investigation as a cognitive enhancing agent due to its ability to increase the P300 amplitude.

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“…This finding may seem paradoxical since it is opposite to the beneficial effects that stimulant medications can have on attention during SD (Bonnet et al, 2005). However, stimulant medication and DA agonists are not always beneficial and in some subjects they impair performance (Oranje et al, 2006). Also, the beneficial effects of stimulant drugs in attention are believed to reflect its dopaminergic as well as its noradrenergic effects on the prefrontal cortex rather than the striatum (Berridge et al, 2006; Corbetta et al, 2008) and to require the stimulation of D1 receptors (or D1 and D2) (Levy, 2008) whereas here we show DA stimulation of D2 receptors in striatum with SD.…”

Section: Discussionmentioning

confidence: 99%

Hyperstimulation of striatal D2 receptors with sleep deprivation: Implications for cognitive impairment

et al. 2009

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Sleep deprivation interferes with cognitive performance but the mechanisms are poorly understood. We recently reported that one night of sleep deprivation increased dopamine in striatum (measured with [11C] raclopride, a PET radiotracer that competes with endogenous dopamine for binding to D2 receptors) and that these increases were associated with impaired performance in a visual attention task. To better understand this association here we evaluate the relationship between changes in striatal dopamine (measured as changes in D2 receptor availability using PET and [11C]raclopride) and changes in brain activation to a visual attention task (measured with BOLD and fMRI) when performed during sleep deprivation versus during rested wakefulness. We find that sleep induced changes in striatal dopamine were associated with changes in cortical brain regions modulated by dopamine (attenuated deactivation of anterior cingulate gyrus and insula) but also in regions that are not recognized targets of dopaminergic modulation (attenuated activation of inferior occipital cortex and cerebellum). Moreover, the increases in striatal dopamine as well as its associated regional activation and deactivation patterns correlated negatively with performance accuracy. These findings therefore suggest that hyperstimulation of D2 receptors in striatum may contribute to the impairment in visual attention during sleep deprivation. Thus, while dopamine increases in prefrontal regions (including stimulation of D1 receptors) may facilitate attention our findings suggest that hyperstimulation of D2 receptors in striatum may impair it. Alternatively, these associations may reflect a compensatory striatal dopamine response (to maintain arousal) that is superimposed on a larger response to sleep deprivation.

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No effects of l-dopa and bromocriptine on psychophysiological parameters of human selective attention

Abstract: Original Papers J Psychopharm

Cited by 20 publications

References 51 publications

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

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

Glutamatergic Modulation of Auditory Information Processing in the Human Brain

Hyperstimulation of striatal D2 receptors with sleep deprivation: Implications for cognitive impairment

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