enkephalin--ala(2)-mephe(4)-gly(5)- and Dystonia

Mu opioid receptor activation modulates acetylcholine release in the dorsal striatum, an area deeply involved in motor function, habit formation, and reinforcement learning as well as in the pathophysiology of different movement disorders, such as dystonia. Although the role of opioids in drug reward and addiction is well established, their involvement in motor dysfunction remains largely unexplored.. We used a multidisciplinary approach to investigate the responses to mu activation in 2 mouse models of DYT1 dystonia (Tor1a. In mutant mice, selective mu receptor activation caused a stronger G-protein-dependent, dose-dependent inhibition of firing activity in cholinergic interneurons when compared with controls. In Tor1a. Mice with the DYT1 dystonia mutation exhibit an enhanced response to mu receptor activation, dependent on selective receptor gene upregulation. Our data suggest a novel role for striatal opioid signaling in motor control, and more important, identify mu opioid receptors as potential targets for pharmacological intervention in dystonia. © 2017 International Parkinson and Movement Disorder Society.

Topics: Acetylcholine; Action Potentials; Adenosine Triphosphate; Analgesics, Opioid; Animals; Calcium; Choline O-Acetyltransferase; Cholinergic Neurons; Corpus Striatum; Disease Models, Animal; Dystonia; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Gene Expression Regulation; Male; Mice; Mice, Transgenic; Molecular Chaperones; Patch-Clamp Techniques; Receptors, Opioid, mu; Somatostatin