Chronic A2A antagonist treatment alleviates parkinsonian locomotor deficiency in MitoPark mice

Neurobiology of Disease
Daniel MarcellinoDagmar Galter

Abstract

Adenosine A(2A) receptor (A(2A)R) antagonists are being investigated as promising treatment strategy for Parkinson's disease (PD). To test whether A(2A)R antagonists are beneficial in early PD stages we used MitoPark mice, a genetic model with gradual degeneration of DA cells. Daily treatment of young MitoPark mice for eight weeks with the A(2A)R antagonist MSX-3 prevented the reduction of spontaneous locomotor activity observed in saline or L-DOPA treated animals. Chronic A(2A)R antagonist treatment neither induced desensitization of receptors nor accumulation of the drug in brain tissue. Despite beneficial effects on behavior, which are not improved upon addition of a low dose of L-DOPA, the characteristic decline of dopamine levels was not changed. Our results indicate that effective dosing with A(2A)R antagonists should be tested as monotherapy in early PD, and serves to remind us that positive behavioral effects of such treatment need not be reflected in rescue of striatal dopamine levels.

References

Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·S FerreK Fuxe
Sep 29, 1999·Progress in Neurobiology·P SvenningssonB B Fredholm
May 20, 2000·JAMA : the Journal of the American Medical Association·G W RossL R White
Apr 18, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marzena Karcz-KubichaSergi Ferré
Aug 13, 2003·Neurology·W Bara-JimenezT N Chase
Aug 13, 2003·Neurology·Robert A HauserUNKNOWN Istradefylline US-001 Study Group
Mar 23, 2004·Brain : a Journal of Neurology·Frédéric CalonThérèse Di Paolo
Jan 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mats I EkstrandNils-Göran Larsson
Feb 21, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Ming YangJohn C Shryock
May 19, 2009·Parkinsonism & Related Disorders·P JennerJ F Chen
Jul 21, 2009·Parkinsonism & Related Disorders·H H FernandezUNKNOWN 6002-US-051 Study Group

❮ Previous
Next ❯

Citations

Oct 26, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Weidong LeJoseph Jankovic
Nov 15, 2011·Behavioural Brain Research·Anna AnvretAndrea Carmine Belin
Apr 9, 2014·Journal of Neuropathology and Experimental Neurology·Silvia CerriMarie Therese Armentero
Sep 17, 2013·Acta Neurologica Scandinavica·I CasettaK Varani
Dec 9, 2014·Expert Opinion on Therapeutic Targets·Kjell FuxeDasiel O Borroto-Escuela
Nov 16, 2010·Behavioural Brain Research·Andrea Carmine BelinDagmar Galter
Mar 13, 2014·Drug Discovery Today·Luca AntonioliGyörgy Haskó
Jan 15, 2019·Journal of Neural Transmission·Dasiel O Borroto-Escuela, Kjell Fuxe
Mar 24, 2021·Experimental Neurology·Michael J Beckstead, Rebecca D Howell

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal ganglia in Parkinson's disease (MDS)

The basal ganglia is comprised of the neostriatum, the external and internal pallidal segments, the subthalamic nucleus, the substantia nigra pars reticulata, and the pars compacta of the substantia nigra. The basal ganglia circuitry is responsible for the correct execution of voluntary movements and is implicated in Parkinson's disease. Here is the latest research investigating the basal ganglia in Parkinson's disease.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

© 2021 Meta ULC. All rights reserved