L-Dopa induced dyskinesias require Cholinergic Interneuron expression of Dopamine 2 receptor
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Background
Striatal Cholinergic Interneurons (CIN) are drivers of L-Dopa induced Dyskinesias (LID). However, what signaling pathways elicit aberrant CIN activity remains unclear. CIN express D2 and D5 receptors suggesting repeated activation of these receptors in response to L-Dopa could promote LID. While the role of D5 in this process has recently been probed, little is known about the role of D2.
Method
Mice with CIN-specific D2 ablation (D2 CIN KO) underwent unilateral 6-OHDA lesion and chronic L-Dopa dosing, throughout which LID severity was quantified. The effect of D2 CIN KO on histological markers of LID severity and CIN activity were also quantified postmortem.
Results
D2 CIN KO attenuated LID across L-Dopa doses, reduced expression of histological LID marker p-ERK, and prevented L-Dopa-induced increases in CIN activity marker p-rpS6 in the dorsolateral striatum.
Conclusion
The activation of D2 specifically on CIN is a key driver of LID.
