RGD Reference Report - Regulation of netrin-1 receptors by amphetamine in the adult brain. - Rat Genome Database

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Regulation of netrin-1 receptors by amphetamine in the adult brain.

Authors: Yetnikoff, L  Labelle-Dumais, C  Flores, C 
Citation: Yetnikoff L, etal., Neuroscience. 2007 Dec 19;150(4):764-73. Epub 2007 Oct 10.
RGD ID: 2314370
Pubmed: PMID:17996376   (View Abstract at PubMed)
PMCID: PMC4880477   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuroscience.2007.09.069   (Journal Full-text)

Netrin-1 is a guidance cue molecule fundamental to the organization of neuronal connectivity during development. Netrin-1 and its receptors, deleted in colorectal cancer (DCC) and UNC-5 homologues (UNC-5), continue to be expressed in the adult brain, although neither their function nor the kinds of events that activate their expression are known. Two lines of evidence suggest a role for netrin-1 in amphetamine-induced dopamine plasticity in the adult. First, DCC is highly expressed by adult dopamine neurons. Second, adult mice with reduced DCC levels do not develop amphetamine-induced behavioral sensitization. To explore the role of netrin-1 in amphetamine-induced plasticity, we examined the effects of sensitizing treatment regimens of amphetamine on DCC and/or UNC-5 protein expression in the adult rat. These treatments produced striking and enduring increases in DCC and UNC-5 expression in the cell body, but not terminal regions, of the mesocorticolimbic dopamine system. Notably, neuroadaptations in the cell body region of mesocorticolimbic dopamine neurons underlie the development of sensitization to the effects of amphetamine. Furthermore, these localized amphetamine-induced changes were prevented by co-treatment with an N-methyl-d-aspartate receptor antagonist, a treatment known to block the development of amphetamine-induced sensitization of behavioral activation, dopamine release and motivated behavior. Using immunohistochemistry, we showed that both DCC and UNC-5 receptors are highly expressed by adult mesocorticolimbic dopamine neurons. These results provide the first evidence that repeated exposure to a stimulant drug such as amphetamine affects netrin-1 receptor expression in the adult brain. Taken together, our findings suggest that changes in netrin-1 receptor expression may play a role in the lasting effects of exposure to amphetamine and other stimulant drugs.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to amphetamine  IEP 2314370 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dcc  (DCC netrin 1 receptor)


Additional Information