ADORA2A and substance dependence: Severe symptoms of opioid withdrawal observed in SWR/J mice were associated with strong transcriptional activation of cytotoxic T lymphocyte-associated protein 2 (Ctla2a) and methionine adenosyltransferase II (Mat2a) genes after acute administration of morphine, whereas changes in gene expression of adenosine A2a receptor (Adora2a) were negatively related to the level of morphine physical dependence across the four inbred mouse strains (Figure 7).