Striatal cholinergic interneurons (SCIN) are the main source of striatal acetylcholine. In Parkinson´s disease (PD), dopaminergic neurons that innervate the striatum degenerate, increasing the cholinergic function that contributes to PD symptoms. The preferred PD therapy is L-dopa administration, but prolonged treatment may result in dyskinesia. Recent studies showing that selective modulation of SCIN activity reduces motor deficits have renewed the interest in understanding the mechanisms that alter SCIN function. SCIN become hyperexcitable in Parkinsonian and dyskinetic mice due to an increased ligand-independent activity of D5 receptors (D5R). Reducing D5R ligand-independent activity with D5 inverse agonists restores SCIN’s physiology. Our aim is to clarify the role of D5R in SCINs activity and evidence the potential therapeutic value of reducing the expression of the D5R in these interneurons. For this, we remove the D5R in SCIN: ChAT-Cre+/-; D5+/+ mice, to induce D5R ablation from all cholinergic neurons during development, and D5+/+ mice injected with a ChAT-Cre viral vector in the striatum after initiation of the L-dopa, which would allow a selective ablation from SCIN in adulthood. Our preliminary results show that L-dopa induces less dyskinesia in KO mice than the control group. Further experiments are needed to confirm these findings and assess the effect of selectively eliminating D5R in SCIN after L-dopa treatment, which could make D5R a therapeutic target for PD.