Objective: The aim of this study is to understand if the antidepressant effect of pramipexole is mediated by D2R or D3R in a mouse model of Parkinson’s disease.

Background: Depression, as a comorbid non-motor symptom, can be observed preceding the motor symptoms in Parkinson’s disease. But mechanisms underlying it are unknown and its current medication is insufficient. The previous study found D3 receptor, a member of D2 like receptor family, expression is decreased in striatum of PD patients. In clinical practice aspect, some kinds of dopamine agonists, especially for pramipexole(PPX) as a dopamine D2/D3 receptor agonist, have an effect on treating Parkinson’s disease-associated depression. But it is not clear whether the action is D3 receptor（D3R）woking with D2 receptor（D2R）together or alone. To find the key to this problem, D2R knock out mice, D3R mutant mice were used in this study.

Method: We used rotarod test and open field test to evaluate motor function of experimental mice. Forced swimming test, tail suspension test and light/dark boxtest were used to examine depressive-like and anxiety symptom of the mice. HPLC was used to determine DA and DOPAC levels in striatum.

Results: The deficiency of D3R mice had a depressive-like and anxiety symptom which was detected by forced swimming test, tail suspension test and light/dark box test. What’s more, the administration of NGB2904, dopamine 2-like receptor antagonist, results the depressive-like behavior in D2R knock out mice which shows the regular emotional behavior before. We found that PPXhas an antidepressant effect for wild type mice in forced swimming test, but not for D3R mutant mice, it indicated PPXhas no effect on treating depression in experimental our mice with dopamine receptor D3 deficiency.

Conclusion: Our results suggested D3R is essential for antidepressant effect of PPX in DA transmitter system and D3R may serve as a therapeutic target for depression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pramipexole-regulates-the-depressive-like-symptom-through-dopamine-d3-not-dopamine-d2-receptor-in-a-mouse-model-of-parkinsons-disease/