Disruption of EphA/ephrin-a signaling in the nigrostriatal system reduces dopaminergic innervation and dissociates behavioral responses to amphetamine and cocaine

Molecular and Cellular Neurosciences
Beth-Anne SieberCarlos F Ibáñez

Abstract

We have investigated functional roles of EphA/ephrin-A signaling in the development and function of the nigrostriatal system by overexpressing a soluble, broad-range EphA receptor antagonist in the central nervous system of transgenic mice. Adult transgenic mice showed a 30-40% reduction in the total volume of the substantia nigra (SN) without detectable differences in the number of dopaminergic neurons. Using fluorogold retrograde tracing from the striatum, we detected a 40-50% reduction in the number of dopaminergic neurons that could be traced from this structure in transgenic mice, suggesting that, a lower proportion of these cells were able to reach the striatum after disruption of EphA/ephrin-A signaling. In spite of this, total dopamine content in the striatum of transgenic mice was comparable to wild type. Analysis of locomotor activity and its regulation by pharmacological treatments that stimulate dopaminergic transmission revealed an unexpected dissociation of the behavioral responses to amphetamine and cocaine. In particular, transgenic mice were relatively insensitive to amphetamine while retaining normal responsiveness to cocaine, which, to the best of our knowledge, represents the first report of a dissociation o...Continue Reading

References

Oct 1, 1977·Acta Pharmacologica Et Toxicologica·S O Ogren, S B Ross
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·P P GaoR Zhou
Dec 1, 1996·Methods : a Companion to Methods in Enzymology·M Brenner, A Messing
Jan 1, 1997·Molecular and Cellular Neurosciences·G Lemke
Apr 8, 1998·Annual Review of Neuroscience·J G Flanagan, P Vanderhaeghen
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·P P GaoR Zhou
Jul 4, 1998·Brain Research. Brain Research Reviews·R R GainetdinovM G Caron
Aug 1, 1998·The Journal of Biological Chemistry·M LackmannA W Boyd
Mar 11, 1999·Current Opinion in Neurobiology·D D O'Leary, D G Wilkinson
Oct 6, 1999·Current Biology : CB·R Klein
Dec 15, 2000·Oncogene·V C Dodelet, E B Pasquale
Jan 9, 2001·Brain Research. Molecular Brain Research·A K HalladayR Zhou
Mar 21, 2001·Nature Reviews. Neuroscience·D G Wilkinson
Feb 20, 2002·Trends in Neurosciences·Bernd Knöll, Uwe Drescher
Apr 26, 2002·Trends in Neurosciences·Johan Holmberg, Jonas Frisén
Feb 1, 1946·The Anatomical Record·M ABERCROMBIE

❮ Previous
Next ❯

Citations

Oct 29, 2011·Genes, Brain, and Behavior·C C ParkerA A Palmer
Jun 19, 2007·PLoS Genetics·Timothy G LesnickDemetrius M Maraganore
Sep 24, 2009·PloS One·Rachel HammondAsa Abeliovich
Apr 13, 2011·PloS One·Brette D BlakelyClare L Parish
Oct 9, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sharon M KolkR Jeroen Pasterkamp
Apr 1, 2014·Neuromolecular Medicine·Shane V HegartyGerard W O'Keeffe
Aug 20, 2010·Biochemical and Biophysical Research Communications·J H SunY M Gao
Jan 22, 2008·Neuroscience and Biobehavioral Reviews·Tamara J PhillipsJeanna M Wheeler
Aug 24, 2007·Neuroscience Letters·Yohtaro NumachiToru Nishikawa
Aug 14, 2009·The European Journal of Neuroscience·Lachlan H ThompsonAnders Björklund
Jun 15, 2007·The European Journal of Neuroscience·A Brent RichardsLawrence F Kromer
Oct 28, 2009·Journal of Neuroscience Research·Elisa TamarizAlfredo Varela-Echavarría
Sep 16, 2015·The International Journal of Neuropsychopharmacology·Monica Dines, Raphael Lamprecht
Apr 23, 2013·Developmental Biology·Shane V HegartyGerard W O'Keeffe
Sep 10, 2014·Behavioural Brain Research·Nathanael J YatesJennifer Rodger
Nov 29, 2007·The Journal of Comparative Neurology·Hebert L Hernández-MontielAlfredo Varela-Echavarría
Nov 13, 2008·Developmental Neurobiology·Margaret A CooperRenping Zhou
Oct 8, 2019·Annals of Clinical and Translational Neurology·Yutaro ObaraKuniaki Ishii
Aug 27, 2010·BMC Neuroscience·Claire DeschampsLaetitia Prestoz
Mar 28, 2009·The Journal of Comparative Neurology·Margaret A CooperRenping Zhou

❮ Previous
Next ❯

Related Concepts

Related Feeds

Researcher Network:CZI Neurodegeneration Challenge

The Neurodegeneration Challenge Network aims to provide funding for and to bring together researchers studying neurodegenerative diseases. Find the latest research from the NDCN grantees here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

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.

Axon Guidance

Axon guidance is a complex neural developmental field that investigates mechanisms through which neurons send out axons to reach its target. Here is the latest research in this domain.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.