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l-dopa and dopamine D2 receptor (D2R) agonists are commonly used to relieve the motor deficits of Parkinson's disease. However, long-term treatment with l-dopa or D2R agonists can induce adverse effects such as abnormal involuntary movements (AIMs), which are major limiting factors in achieving long-term control of parkinsonian syndromes. The pathophysiological mechanisms involved in the development of dopaminergic agonist-induced adverse effects are not well understood. Here, we examined the role of two D2R isoforms, D2S and D2L, in l-