Blockade of M4 muscarinic receptors on striatal cholinergic interneurons normalizes striatal dopamine release in a mouse model of TOR1A dystonia
Anthony M. Downs, Yuping Donsante, Hyder A. Jinnah, Ellen J. Hess
Abstract
KI mice. Further, we found that the subtype selective M4 antagonist VU6021625 recapitulates the effects of THP. These data implicate a principal role for M4 mAChR located on striatal cholinergic interneurons in the mechanism of action of THP and suggest that subtype selective M4 mAChR antagonists may be effective therapeutics with fewer side effects than THP for the treatment of TOR1A dystonia.
Topics & Concepts
DystoniaMuscarinic acetylcholine receptorCholinergicDopamineNeuroscienceAntagonistPharmacologyDopamine receptor D2Muscarinic antagonistBiologyMedicineReceptorInternal medicineNeurological disorders and treatmentsGenetic Neurodegenerative DiseasesNeuroscience and Neuropharmacology Research