COMT Inhibition by Tolcapone Further Improves Levodopa Pharmacokinetics when Combined with a Dual-Release Formulation of Levodopa/Benserazide

Gasser, Urs; Jorga, Karin; Crevoisier, C; Hovens, S.E.L.; Giersbergen, Paul L. M. van

doi:10.1159/000008052

Cited by 16 publications

(6 citation statements)

References 13 publications

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“…Prior to completing the task, each participant signed the consent form and completed the MMSE. Testing OFF medication took place after a 12 h withdrawal period after which L-DOPA blood plasma concentrations are reduced to zero [27,28]. …”

Section: Methodsmentioning

confidence: 99%

Dopaminergic modulation of the updating of stimulus–response episodes in Parkinson's disease

Colzato

Wouwe

Zmigrod

et al. 2012

Behavioural Brain Research

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Increasing evidence suggests that the control of retrieval of episodic feature bindings is modulated by the striatal dopaminergic pathway. The present study investigated whether this may reflect a contribution from the ventral or the dorsal part of the striatum. Along the lines of the overdose hypothesis in Parkinson’s disease (PD), functions known to rely on the dorsal striatum are enhanced with dopaminergic medication, while operations relying on the ventral circuitry are impaired. We found that partial mismatches between present and previous stimulus–response relations are, compared to control participants, abnormally low OFF DA medication and normalized ON DA medication. The results suggest that the dorsal striatum, but not (or not so much) the ventral striatum, is driving the flexible control of retrieval of stimulus–response episodes.

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Section: Methodsmentioning

confidence: 99%

Dopaminergic modulation of the updating of stimulus–response episodes in Parkinson's disease

Colzato

Wouwe

Zmigrod

et al. 2012

Behavioural Brain Research

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“…As well, each participant completed the pegboard and finger tapping tasks ON and OFF medication. Testing OFF medication took place after a 12 h withdrawal period after which L-dopa blood plasma concentrations are reduced to zero (Crevoisier, Monreal, Metzger, & Nilsen, 2003; Gasser, Jorga, Crevoisier, Hovens, & van Giersbergen, 1999). Note however that DA agonists are associated with a longer half-life, which may have resulted in some residual medication effects.…”

Section: Methodsmentioning

confidence: 99%

Dose dependent dopaminergic modulation of reward-based learning in Parkinson's disease

et al. 2012

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Learning to select optimal behavior in new and uncertain situations is a crucial aspect of living and requires the ability to quickly associate stimuli with actions that lead to rewarding outcomes. Mathematical models of reinforcement-based learning to select rewarding actions distinguish between (1) the formation of stimulus–action–reward associations, such that, at the instant a specific stimulus is presented, it activates a specific action, based on the expectation that that particular action will likely incur reward (or avoid punishment); and (2) the comparison of predicted and actual outcomes to determine whether the specific stimulus–action association yielded the intended outcome or needs revision. Animal electrophysiology and human fMRI studies converge on the notion that dissociable neural circuitries centered on the striatum are differentially involved in different components of this learning process. The modulatory role of dopamine (DA) in these respective circuits and component processes is of particular relevance to the study of reward-based learning in patients diagnosed with Parkinson's disease (PD). Here we show that the first component process, learning to predict which actions yield reward (supported by the anterior putamen and associated motor circuitry) is impaired when PD patients are taken off their DA medication, whereas DA medication has no systematic effects on the second processes, outcome evaluation (supported by caudate and ventral striatum and associated frontal circuitries). However, the effects of DA medication on these processes depend on dosage, with larger daily doses leading to a decrease in predictability of stimulus–action–reward relations and increase in reward-prediction errors.

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“…H. H. was not involved in the behavioral testing, but was available in case of medical emergencies and provided decoding information to the main investigator (P. K.) after all participants had been tested. A dual-release formulation of 200 mg levodopa/50 mg benserazide (Madopar DR; Roche Pharma AG, Reinach, Switzerland) with a fast absorption within the first hour and sustained concentration levels thereafter (Gasser, Jorga, Crevoisier, Hovens, & van Giersbergen, 1999) was administered. Each participant had been strictly instructed to refrain from any food intake between noon and the beginning of the experiment at 3:30 pm.…”

Section: L-dopa Administrationmentioning

confidence: 99%

Dopamine, Paranormal Belief, and the Detection of Meaningful Stimuli

Kempler

Möhr

Haker³

et al. 2010

Journal of Cognitive Neuroscience

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Dopamine, paranormal belief, and the detection of meaningful stimuliKrummenacher, P; Mohr, C; Haker, H; Brugger, P Krummenacher, P; Haker, H; Brugger, P (2010 Abstract ■ Dopamine (DA) is suggested to improve perceptual and cognitive decisions by increasing the signal-to-noise ratio. Somewhat paradoxically, a hyperdopaminergia (arguably more accentuated in the right hemisphere) has also been implied in the genesis of unusual experiences such as hallucinations and paranormal thought. To test these opposing assumptions, we used two lateralized decision tasks, one with lexical (tapping left-hemisphere functions), the other with facial stimuli (tapping right-hemisphere functions). Participants were 40 healthy righthanded men, of whom 20 reported unusual, "paranormal" experiences and beliefs ("believers"), whereas the remaining participants were unexperienced and critical ("skeptics"). In a between-subject design, levodopa (200 mg) or placebo administration was balanced between belief groups (double-blind procedure). For each task and visual field, we calculated sensitivity in the placebo group. Criterion analyses revealed that believers favored false alarms over misses, whereas skeptics displayed the opposite preference. Unexpectedly, under levodopa, these decision preferences were lower in both groups. We thus infer that levodopa (1) decreases sensitivity in perceptual-cognitive decisions, but only in skeptics, and (2) makes skeptics less and believers slightly more conservative. These results stand at odd to the common view that DA generally improves signal-to-noise ratios. Paranormal ideation seems an important personality dimension and should be assessed in investigations on the detection of signals in noise. ■

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COMT Inhibition by Tolcapone Further Improves Levodopa Pharmacokinetics when Combined with a Dual-Release Formulation of Levodopa/Benserazide

Cited by 16 publications

References 13 publications

Dopaminergic modulation of the updating of stimulus–response episodes in Parkinson's disease

Dopaminergic modulation of the updating of stimulus–response episodes in Parkinson's disease

Dose dependent dopaminergic modulation of reward-based learning in Parkinson's disease

Dopamine, Paranormal Belief, and the Detection of Meaningful Stimuli

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