bFGF expression is differentially regulated by cocaine seeking versus extinction in learning-related brain regions

Abstract

In cocaine use disorder, relapse can be elicited by drug-associated cues despite long periods of abstinence. The persistence of drug-associated cues in eliciting drug seeking suggests enduring changes in structural and functional plasticity, which may be mediated by basic fibroblast growth factor (bFGF, FGF2). Stimulant drug use increases bFGF expression in reward- and learning-related brain regions, such as the infralimbic medial-prefrontal cortex (IL-mPFC), and we previously found that this increase was reversed by extinction. However, whether bFGF expression is similarly modified in other brain regions is unknown. Therefore, we used the conditioned place preference (CPP) paradigm to assess bFGF expression following cocaine-associated CPP or extinction of that CPP within the mPFC, nucleus accumbens (NAc), hippocampus (Hipp), and basolateral amygdala (BLA). bFGF expression was increased in IL-mPFC and NAc-Core and -Shell following a cocaine-associated CPP, an effect reversed by extinction. Conversely, bFGF expression was increased in BLA following extinction, but no significant changes were observed in PL-mPFC or either dorsal or ventral Hipp. These results demonstrate differential regulation of bFGF following cocaine-associated CPP or extinction of that CPP in discrete brain regions. Changes in bFGF expression may regulate long-lasting drug-induced plasticity that underlies persistent drug-associated memories, and therefore present potential prophylactic targets.

New developments in the biology of fibroblast growth factors

“…These results indicate that cocaine‐induced overexpression of FGF2 inhibits extinction and blocking FGF2 enhances extinction (Hafenbreidel et al, 2015). Fgf2 expression is altered in a region‐specific manner following cocaine‐seeking and extinction in rats, indicating that FGF2 uniquely mediates drug seeking and extinction in specific brain regions (Doncheck et al, 2018). These and other results indicate that cocaine increases FGF2 levels in several mesocorticolimbic brain regions, and that FGF2 levels positively correlate with cocaine consumption and sensitization.…”