A Role for the Fibroblast Growth Factor System in Cocaine Sensitization
Gula, E.; Flagel, S.B.; Turner, C.A.; Watson, S.J.; Akil, H
Society for Neuroscience. 2006.
The fibroblast growth factor (FGF) system has been implicated in psychiatric illness and, most recently, addiction research. We have previously shown that neonatal injections of FGF2 result in long-term morphological and gene expression changes in the hippocampus, a region largely known for its role in affective disorders. The present set of studies examined the interaction between the FGF system and cocaine sensitization. We assessed alterations in FGF gene expression after a sensitizing regimen of cocaine, as well as the effects of early life FGF2 (20ng/g) administration on behavioral sensitization to cocaine in adulthood. We also assessed the effects of early life FGF2 on dopamine transcripts (DAT, TH, D1 and D2) in adulthood in the substantia nigra, ventral tegmental area, nucleus accumbens and striatum by in situ hybridization. We found no changes in the dopamine system after early life FGF2. However, the FGF system was significantly altered after cocaine sensitization in the hippocampus, amygdala, and prefrontal cortex. Preliminary studies also suggest that early life FGF2 alters behavioral sensitization to cocaine in adulthood. We are continuing to investigate the effects of this early life treatment on drug-taking behavior. These results suggest that the FGF system may play a role substance abuse. Furthermore, these studies highlight a role for the hippocampus in addiction. Supported by Conte Center Grant #L99MH60398, NIH Grant No. 5 P01 MH42251, RO1 DA13386 and Office of Naval Research (ONR) N00014-02-1-0879 to HA & SJW.