The response of the brain to addictive substances such as nicotine includes the rapid induction of genes that influence synaptic events. This response is different in adolescent brain, which continues to undergo synaptic remodeling in regions that include reward-associated corticolimbic areas. We report here that acute nicotine (0.4 mg/kg), but not cocaine or exposure to a novel environment, induces the expression of the dendritically targeted, corticolimbic mRNA Dendrin in specific regions of adolescent brain. Acute nicotine resulted in an increase in Dendrin mRNA levels in the adolescent prefrontal cortex that was not evident in adult animals. The induction in Dendrin mRNA was a rapid, short-lived transcriptional event that resulted in changes in Dendrin protein. For example, an increase in Dendrin protein levels following nicotine treatment paralleled enhanced Dendrin immunoreactivity in the dendrites of pyramidal neurons of somatosensory cortex. As Dendrin is an important component of cytoskeletal modifications at the synapse, these results suggest that nicotine influences unique plasticity-related changes in the adolescent forebrain that differ from the adult.