Clinical correlates of 6-hydroxydopamine injections into A11 dopaminergic neurons in rats: A possible model for restless legs syndrome?

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Abstract
Pursuant to the clinical suspicion that restless legs syndrome (RLS) may involve dopaminergic diencephalic spinal neurons (A11), we performed stereotaxic bilateral 6‐hydroxydopamine (6‐OHDA) lesions into the A11 nucleus to observe for any behavioral correlates similar to this clinical condition. Pathologic examination demonstrated a 54% reduction in A11 tyrosine hydroxylase staining cells in rats injected with 6‐OHDA versus sham treatment. Multiple blindly rated 90–120‐minute video epochs demonstrated an increased average number of standing episodes (14.4 ± 11.7 versus 7.3 ± 5.5 episodes/epoch) and increased total standing time (38.9 ± 20.5 versus 25.3 ± 12.2 minutes/epoch) but similar total sleep time in four lesioned rats when compared with two sham rats. Treatment of the lesioned rats with intramuscular pramipexole subsequently resulted in fewer standing episodes (4.4 ± 3.3 versus 14.4 ± 11.7 episodes/epoch) and less total standing time (20.9 ± 12.3 versus 38.9 ± 20.5 minutes/epoch) when compared with untreated lesioned rats. Despite a large number of observations, the small number of lesioned animals precluded formal statistical analysis. These behaviors are consistent, although not specific, with what would be expected in an animal model of RLS.