The effects of cocaine treatment on alternative splicing have received little attention. However, acute exposure to cocaine is known to alter splicing of transcripts encoded by the rat BDNF gene [56]. BDNF, acting through its TrkB receptor, plays an important role in the behavioral response to cocaine and enhances responsiveness to glutamate [57-59]. Cocaine- and activity-regulated alternative splicing of the Homer family of scaffolding proteins also affects synaptic signaling [43,60]. For Kalrn, splicing events that lead to the inclusion of different 3'-terminal exons produce proteins with distinctly different functions. Since the GEF2 region of Kalirin can be activated upon binding Gαq [61], leading to activation of RhoA, even a slight shift in the ratio of isoforms with both GEF domains vs GEF1 alone should be of significance. Cocaine-induced alternative splicing of Kalrn transcripts may be important in the biochemical and/or behavioral response to cocaine.
