Motor learning-related gene regulation in the striatum: Effects of cocaine

We investigated the relationship between changes in gene regulation in the striatum and motor learning under the influence of cocaine. Rats were trained oil a running wheel for up to 8 days. One day after the training, enduring molecular changes were mapped throughout the striatum. Running-wheel training affected several molecule classes. Challenge-induced expression of the transcription factor c-fos, the synaptic plasticity factor Homer 1 and the neuropeptide substance P (but not enkephalin) was enhanced relative to cocaine-treated, non-running controls. These molecular changes were associated with the training phase when rats learn to run on the wheel; they were present after the first training session, peaked after day 2, decreased by day 4, and were absent after 8 days of training. These effects were most robust in the dorsal sensorimotor striatum that receives inputs from the medial agranular (premotor) and sensorimotor cortex. Borderline training effects (c-fos, Homer 1) were found when rats trained without cocaine treatment. These findings indicate that motor learning is associated with transiently enhanced inducibility of genes that may participate in restructuring of transstriatal circuits. Cocaine appears to abnormally enhance or alter such learning-related molecular changes. Future studies will have to determine whether these molecular changes are related to motor memory consolidation or other processes of motor learning.