[Show abstract][Hide abstract] ABSTRACT: The development of an impulse control disorder (ICD) is now recognized as a potential nonmotor adverse effect of dopamine replacement therapy in Parkinson's disease (PD). Here, recent epidemiological, neurophysiological and genetic advances are summarized to outline potential mechanisms involved. It is safe to say that dopaminergic drugs, particularly dopamine agonists, are able to induce ICDs only in a minority of patients, while the majority are somehow protected from this adverse effect. While it seems clear that men with early-onset PD are more vulnerable, other predisposing factors, such as various current or pre-PD personality traits, are a matter of debate. In terms of neurophysiological advances, one may find striking analogies to the addiction literature suggesting a causal chain beginning with certain predisposing conditions of striatal dopamine synapses, an "unnatural" increase of dopamine stimulation and a characteristic pattern of resulting functional changes in remote networks of appetitive drive and impulse control. Future prospects include potential add-on medications and the possible identification of genetic predispositions at a genome-wide scale. Functional imaging of pharmacogenetic interactions (imaging pharmacogenomics) may be an important tool on that road.
Brain Structure and Function 05/2011; 216(4):289-99. DOI:10.1007/s00429-011-0314-0 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the cardinal manifestations of Parkinson's disease (PD) are attributed to a decline in dopamine levels in the striatum, a breadth of non-motor features and treatment-related complications in which the serotonergic system plays a pivotal role are increasingly recognised. Serotonin (5-HT)-mediated neurotransmission is altered in PD and the roles of the different 5-HT receptor subtypes in disease manifestations have been investigated. The aims of this article are to summarise and discuss all published preclinical and clinical studies that have investigated the serotonergic system in PD and related animal models, in order to recapitulate the state of the current knowledge and to identify areas that need further research and understanding.
Progress in Neurobiology 08/2011; 95(2):163-212. DOI:10.1016/j.pneurobio.2011.08.004 · 10.30 Impact Factor
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