However, this notion per se could not explain the progressive increase in the severity of LID, which occurs in the PD patients treated with unaltered dosages of given dopaminergic drugs (Brotchie, 2005), because there is an ongoing decline in striatal responsiveness to D1R activation along a repeated exposure to levodopa under the conditions of PD, as determined by fos induction experiments (Saka et al., 1999; Kashihara et al., 2000; Xu et al., 2003; Morigaki et al., 2017). This evidence concerns the gene FOS and Parkinson disease.