RT Journal Article
SR Electronic
T1 Role of netrin-1 in the organization and function of the mesocorticolimbic dopamine system
JF Journal of Psychiatry and Neuroscience
JO J Psychiatry Neurosci
FD Canadian Medical Association
SP 296
OP 310
DO 10.1503/jpn.100171
VO 36
IS 5
A1 Cecilia Flores
YR 2011
UL http://jpn.ca/content/36/5/296.abstract
AB Changes in mesocorticolimbic dopamine (DA) neurons and their target cells can be induced throughout life and are important determinants of individual differences in susceptibility to psychopathology. The goal of my research is to gain insight into the nature of the cellular and molecular mechanism underlying the selective plasticity of mesocorticolimbic DA neurons. Here, I review work showing that the guidance cue netrin-1 is implicated in the organization, plasticity and function of mesocorticolimbic DA neurons in rodents. Developmental variations in netrin-1 receptor function result in selective reorganization of medial prefrontal DA circuitry during adolescence and in an adult phenotype protected against schizophrenia-like dopaminergic and behavioural abnormalities. Furthermore, in adulthood, expression of netrin-1 receptors is upregulated by repeated exposure to stimulant drugs of abuse in DA somatodendritic regions and is necessary for drug-induced behavioural plasticity. I propose that risk factors associated with DA-related adult psychiatric disorders alter netrin-1 function.