Cell adhesion signaling pathways: First responders to cocaine exposure?

The 100 billion neurons comprising the human brain are wired together using structural extensions termed axons, dendrites and dendritic spines. Addictive drugs remodel dendritic spine structure in certain brain regions and with repeated exposure, induce psychomotor sensitization and impair behavioral flexibility. We recently reported that low-dose cocaine exposure, in combination with knockout of Arg-an adhesion-regulated nonreceptor tyrosine kinase that stabilizes neuronal shape starting in adolescence-recapitulates both features of chronic drug exposure in rodents. In light of these and other recent findings in the field, we suggest that cell adhesion receptors and their downstream cytoskeletal effectors act as "first responders" to psychostimulant exposure. In this model, cell adhesion factors act to stabilize existing dendritic spines in response to cocaine, and reduced expression/function is expected to increase vulnerability. Moreover, this model anticipates that increased sensitivity to psychostimulants in adolescence relates to neuronal pruning processes that occur during this developmental period.