Li et al. performed an analysis on peer-reviewed literature, spanning 30 years, that linked genes to addiction in an attempt to uncover new molecular pathways that contribute to addiction. The authors acknowledged that pathways are subjective concepts; however, their analysis did identify pathways previously implicated in addiction and also suggested that gonadotropin-releasing hormone signaling and gap junction signaling may contribute as well. Their analysis of pathways associated with four different addictive classes of drugs led to the development of a hypothetical molecular network based on these pathways and additional protein interaction data. Systems analysis of the "addiction" network suggested that calcium/calmodulin-dependent protein kinase II (CaMKII) may be a central regulator with two "fast" positive-feedback loops (based on second messenger and downstream effector signaling) and two "slow" positive-feedback loops (based on gene transcription and translation) interlinking through CaMKII. Although the predictions were not confirmed experimentally, the analysis points toward experimentally testable hypotheses, and the associated database provides a tool for addiction researchers.
C.-Y. Li, X. Mao, L. Wei, Genes and (common) pathways underlying drug addiction. PLoS Comput. Biol. 4, e2 (2008). [PubMed]