http://repub.eur.nl/res/aut/42438/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/38532/ 2012-11-27T00:00:00Z Contemporary theoretical models of substance dependence posit that deficits in inhibitory control play an important role in substance dependence. The neural network underlying inhibitory control and its association with substance dependence have been widely investigated. However, the pharmacology of inhibitory control is still insufficiently clear. The aims of the current study were twofold. First, we investigated the role of dopamine in inhibitory control and associated brain activation. Second, the proposed link between dopamine and impaired inhibitory control in nicotine dependence was investigated by comparing smokers and non-smoking controls. Haloperidol (2 mg), a dopamine D2/D3 receptor antagonist, and placebo were administered to 25 smokers and 25 non-smoking controls in a double-blind randomized cross-over design while performing a Go/NoGo task during fMRI scanning. Haloperidol reduced NoGo accuracy and associated brain activation in the ACC, right SFG and left IFG, showing that optimal dopamine levels are crucial to effectively implement inhibitory control. In addition, smokers showed behavioral deficits on the Go/NoGo task as well as hypoactivity in the left IFG, right MFG and ACC after placebo, supporting the hypothesis of a hypoactive prefrontal system in smokers. Haloperidol had a stronger impact on prefrontal brain activation in non-smoking controls compared to smokers, which is in line with the inverted 'U' curve theory of dopamine and cognitive control. The current findings suggest that altered baseline dopamine levels in addicted individuals may contribute to the often observed reduction in inhibitory control in these populations. http://repub.eur.nl/res/pub/28908/ 2008-01-01T00:00:00Z Introduction: Several theoretical accounts of the role of dopamine suggest that dopamine has an influence on the processing of affective stimuli. There is some indirect evidence for this from studies showing an association between the treatment with dopaminergic agents and self-reported affect. Materials and methods: We addressed this issue directly by examining the electrophysiological correlates of affective picture processing during a single-dose treatment with a dopamine D2 agonist (bromocriptine), a dopamine D2 antagonist (haloperidol), and a placebo. We compared early and late event-related brain potentials (ERPs) that have been associated with affective processing in the three medication treatment conditions in a randomized double-blind crossover design amongst healthy males. In each treatment condition, subjects attentively watched neutral, pleasant, and unpleasant pictures while ERPs were recorded. Results: Results indicate that neither bromocriptine nor haloperidol has a selective effect on electrophysiological indices of affective processing. In concordance with this, no effects of dopaminergic modulation on self-reported positive or negative affect was observed. In contrast, bromocriptine decreased overall processing of all stimulus categories regardless of their affective content. Discussion: The results indicate that dopaminergic D2 receptors do not seem to play a crucial role in the selective processing of affective visual stimuli. http://repub.eur.nl/res/pub/7396/ 1990-04-19T00:00:00Z http://repub.eur.nl/res/pub/37477/ 1983-04-20T00:00:00Z Psychiatrists are frequently confronted with psychoses that are difficult to classify. Many forms of these atypical psychoses have been described in European literature. They often have an acute onset and a tendency towards complete remission, albeit with an episodic course. Rich, multiform symptomatology is noted sometimes in addition to altered states of consciousness. In patients with a grossly impaired consciousness the psychiatrist has also to consider whether such a psychosis is due to organic factors or is functional (I). Even when morphologically demonstrable organic factors are excluded, the possibility of a reaction of the brain to subtle toxic factors disturbing the normal physico-chemical equilibrium without causing cellular damage has to be taken into account. An intermittent production of such toxins in the brain or the liver has been an attractive concept for many researchers to understand and account for the endogenous functional psychoses (2). In this thesis an attempt is made to provide clinical evidence for the endogenous synthesis of toxic factors which are causally related to some types of the atypical psychoses. The findings have led to a new classification of the group of poorly defined and previously unclassifiable psychoses.