Given its role in the development of thalamocortical projections and its general distribution in areas thought to be important in addiction , it is not surprising that NRCAM was hypothesized to play a role in addiction.
As discussed above, one of the reverse translational approaches used to confirm the possibility that variation in the NRCAM gene may contribute to addiction was the use of Nrcam KO mice.
Using the same logic as was previously described for NRCAM , Cdh13 KO mice were used to examine the effects of alterations in Cdh13 expression on addiction-related phenotypes .
PTPRD addiction-related haplotypes were shown to correlate with mRNA levels in human brain samples , providing the same sort of logic for examining drug responses in Ptprd-deficient mice (e.g., Ptprd KO mice) as for Nrcam and Cdh13.
Few changes in overall transcript expression were observed in these mice, but there were substantial changes in the relative abundance of particular transcripts, including genes involved in membrane excitability (Gabrg2, Grin1, Scn8a, and Snap25), but also the CAMs Nrcam and Nrxn3.
Studies in genetically modified mice have shown that reductions in the expression of several CAM genes, including NRCAM , CDH13 , CSMD1 , and PTPRD , affect responses to drugs of abuse, particularly cocaine, in standard animal models of psychostimulant responses that are important in the study of addictive properties of abused drugs.
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Gong et al., "NrCAM in addiction vulnerability: positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice," Neuropsychopharmacology, vol.
Lee et al., "Association of the neuronal cell adhesion molecule (NrCAM) gene variants with personality traits and addictive symptoms in methamphetamine use disorder," Psychiatry Investigation, vol.