Impulse control disorders in Parkinson's disease: seeking a roadmap toward a better understanding.
Bottom Line: 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.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.
Affiliation: Parkinson Institute, Istituti Clinici di Perfezionamento, via Bignami 1, 20126 Milan, Italy. email@example.comShow MeSH
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Mentions: As mentioned before, DAA may increase appetitive drive (novelty seeking and impulsivity) while hampering negative feedback learning and behavioral inhibition. However, only a minority of PD patients actually develop ICD behaviors, suggesting an individual predisposition. One can only speculate on the underlying pharmacophysiologic–psychological interactions that drive behavioral change in susceptible patients. On the assumption of a relatively increased synaptic dopamine level in the striatum of vulnerable PD patients, we derive hypotheses based and an established model of the effects of tonic and phasic dopamine release on cortical connections with the direct and indirect pathways of the basal ganglia (Fig 2a). Decision making is believed to involve interactions of inhibitory and motivational inputs to the ventral striatum that are modified by convergent dopaminergic innervation from the ventral tegmental area (Goto et al. 2007). Phasic dopamine release, via D1 receptor activation, has been shown to facilitate inputs from motivational areas (e.g., medial OFC, frontopolar cortex) and thereby strengthens the influence of the direct or ‘Go’ pathway on executive areas (Goto and Grace 2005). Conversely, a transient reduction of tonic dopamine release, via D2-receptor inactivation, increases inputs from inhibitory areas (e.g., vlPFC and ACC) and thereby strengthens the influence of the indirect or ‘NoGo’ pathway on areas of executive control (Goto and Grace 2005).Fig. 2
Affiliation: Parkinson Institute, Istituti Clinici di Perfezionamento, via Bignami 1, 20126 Milan, Italy. firstname.lastname@example.org