Background
Parkinsonism is caused by dopamine (DA) insufficiency and
Conclusions
The work suggests that pharmacological modulation of ChIs by β-ARs might provide a therapeutic option for managing LID.
Methods
We used conditional Slc6a3DTR/+ mice to model progressive DA deficiency and the β-adrenergic receptor (β-AR) antagonist propranolol to limit the activity of striatal cholinergic interneurons (ChIs). DA-deficient mice were treated with L-Dopa and the dopa decarboxylase inhibitor benserazide. LID and motor performance were assessed by rotarod, balance beam, and open field testing. Electrophysiological experiments characterized the effects of β-AR ligands on striatal ChIs.
Results
LID was observed in a subset of DA-deficient mice. Treatment with propranolol relieved LID and motor hyperactivity. Electrophysiological experiments showed that β-ARs can effectively modulate ChI firing. Conclusions: The work suggests that pharmacological modulation of ChIs by β-ARs might provide a therapeutic option for managing LID.