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

The basal ganglia are thought to modulate the release or inhibition of move ments 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 o f 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 bet ween these matrix-based pathways and the striosomal pathway regulates the f requency of release of given behavioral sequences and, thus, modulates beha vioral focus. Differential plasticity in these compartmentally organized ci rcuits might contribute to the development of L-dopa-induced dyskinesias un der parkinsonian conditions and dopamine-receptor-agonist induced stereotyp ies under normal conditions.