05888.Abstract NETRIN-1 RECEPTOR-DEFICIENT MICE SHOW ENHANCED MESOCORTICAL DOPAMINE TRANSMISSION AND BLUNTED BEHAVIOURAL RESPONSES TO AMPHETAMINE Alanna Grant, Daniel Hoops, Cassandre Labelle-Dumais, Michael Prvost, Heshmat Rajabi, Bryan Kolb, Jane Stewart, Andreas Arvanitogiannis and Cecilia Flores 1Douglas Mental Health University Institute, Department of Psychiatry, McGill University, 6875 LaSalle Boulevard, Verdun, Quebec, Canada, H4H 1R3 2Center for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec, Canada 3Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada Dr Cecilia Flores, as above.ABSTRACT The mesocorticolimbic dopamine (DA) system is implicated in neurodevelopmental psychiatric disorders including schizophrenia but it is unknown how disruptions in brain development modify this system and increase predisposition to cognitive and behavioural abnormalities in adulthood.Are guidance cues involved in the proper organization of neuronal connectivity during development.Have hypothesized that variations in the function of DCC (deleted in colorectal cancer), a netrin-1 receptor highly expressed by DA neurones, may result in altered development and organization of mesocorticolimbic DA circuitry, and influence DA function in the adult.Test this hypothesis, we assessed the effects of reduced DCC on several indicators of DA function._in-vivo_ microdialysis, we showed that adult mice that develop with reduced DCC display increased basal DA levels in the medial prefrontal cortex and exaggerated DA release in response to the indirect DA agonist amphetamine.Contrast, these mice exhibit normal levels of DA in the nucleus accumbens but significantly blunted amphetamine-induced DA release.Using conditioned place preference, lotor activity and prepulse inhibition paradigms, we found that reduced DCC diminishes the rewarding and behavioural-activating effects of amphetamine and protects against amphetamine-induced deficits in sensorimotor gating.We found that adult DCC-deficient mice exhibit altered dendritic spine density in layer V medial prefrontal cortex pyramidal neurones but not in nucleus accumbens medium spiny neurones.Findings demonstrate that reduced DCC during development results in a behavioural phenotype opposite to that observed in developmental models of schizophrenia and identify DCC as a critical factor in the development of DA function.USERS WHO READ THIS ARTICLE ALSO READ: Alpha-synuclein In The Nucleus Accumbens Induces Changes In Cocaine Behaviour In Rats Frederic Boyer and Jean-Luc DreyerEuropean Journal of Neuroscience, Volume 26, Issue 10, Page 2764-2776, Nov 2007, doi: 10.05878. Repeated Exposure To Cocaine Differently Modulates BDNF MRNA And Protein Levels In Rat Striatum And Prefrontal Cortex Fabio Fumagalli, Laura Di Pasquale, Lucia Caffino, Giorgio Racagni and Marco Andrea RivaEuropean Journal of Neuroscience, Volume 26, Issue 10, Page 2756-2763, Nov 2007, doi: 10.05918. Acetaldehyde Mediates Alcohol Activation Of The Mesolimbic Dopamine System M.P.T.And M.Journal of Neuroscience, Volume 26, Issue 10, Page 2824-2833, Nov 2007, doi: 10.05887. Phenotype Of V2-derived Interneurons And Their Relationship To The Axon Guidance Molecule EphA4 In The Developing Mouse Spinal Cord Line Lundfald, C.Restrepo, Simon J.Butt, Chian-Yu Peng, Steven Droho, Toshiaki Endo, Hanns Ulrich Zeilhofer, Kamal Sharma, and Ole KiehnEuropean Journal of Neuroscience, Volume 26, Issue 11, Page 2989-3002, Dec 2007, doi: 10.05906. Towards Therapy To Relieve Memory Impairment After Anterior Thalamic Lesions: Improved Spatial Working Memory After Immediate And Delayed Postoperative Enrichment Elena A.Mark C.James P.Mathieu Wolff and John C.Journal of Neuroscience, Volume 26, Issue 11, Page 3267-3276, Dec 2007, doi: 10.05879. Context Modulates The Expression Of Conditioned Motor Sensitization, Cellular Activation And Synaptophysin Immunoreactivity David J.T.Napier and Gloria E.Journal of Neuroscience, Volume 26, Issue 9, Page 2661-2668, Nov 2007, doi: 10.Read more
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