TY - JOUR T1 - Forced Nonuse in Unilateral Parkinsonian Rats Exacerbates Injury JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6790 LP - 6799 DO - 10.1523/JNEUROSCI.22-15-06790.2002 VL - 22 IS - 15 AU - Jennifer L. Tillerson AU - Ann D. Cohen AU - W. Michael Caudle AU - Michael J. Zigmond AU - Timothy Schallert AU - Gary W. Miller Y1 - 2002/08/01 UR - http://www.jneurosci.org/content/22/15/6790.abstract N2 - Diagnosis of Parkinson's disease (PD) is based on the presentation of clinical symptoms such as bradykinesia, resting tremor, and rigidity. However, one feature of PD that often begins years before diagnosis is decreased physical activity. We hypothesized that this depressed activity is not only a symptom of the early dopaminergic loss but also a catalyst in the degenerative process. Two experiments were performed to test this hypothesis. First, rats were exposed to a mild dose of 6-hydroxydopamine unilaterally into the nigrostriatal dopamine (DA) projections, which would normally result in an ∼20% DA loss and no detectable behavioral asymmetries. A subset of these lesioned animals then had a cast applied for 7 d to the contralateral forelimb. After the cast was removed, these animals displayed long-term behavioral asymmetry and exacerbation of neurochemical loss (∼60% depletion). Second, a group of animals received a high dose of 6-hydroxydopamine that normally would yield a severe loss of nigrostriatal terminals (∼90% loss) and chronic sensorimotor deficits. During the first 7 d after neurotoxin exposure, a subset of these animals were forced to rely on the contralateral forelimb, a procedure we have previously reported to protect DA terminals and behavioral function. Some of these rats then had the use of their “recovered” forelimb restricted during the second or third week after lesioning. This precipitated a severe and chronic loss of DA terminals and functional deficits. These results suggest decreased physical activity not only is a symptom of PD but also may act to potentiate the underlying degeneration. ER -