Levodopa-induced dyskinesias and dopamine-dependent stereotypies: a new hypothesis

The basal ganglia are thought to modulate the release or inhibition of movements by way of direct and indirect pathways that act as a push-pull system of cortico-basal ganglia circuits. Here we suggest a three-pathway model of the basal ganglia that takes into consideration the fundamental division of the striatum into striosomes and extrastriosomal matrix. We suggest that, in addition to the balance between direct and indirect pathways on which normal release of individual movements depends, the balance of activity between these matrix-based pathways and the striosomal pathway regulates the frequency of release of given behavioral sequences and, thus, modulates behavioral focus. Differential plasticity in these compartmentally organized circuits might contribute to the development of L-dopa-induced dyskinesias under parkinsonian conditions and dopamine-receptor-agonist induced stereotypies under normal conditions.