Stress and cocaine interact to modulate basic fibroblast growth factor (FGF-2) expression in rat brain.
BACKGROUND
Our laboratory has previously demonstrated that the expression of basic fibroblast growth factor (FGF-2), a protein involved in survival and maintenance of several cell phenotypes as well as in synaptic plasticity, is modulated by stress (Molteni et al., Brain Res Rev 37:249-258, 2001; Fumagalli et al., Neurobiol Dis 20:731-737, 2005) and cocaine (Fumagalli et al., J Neurochem 96:996-1004, 2006).


OBJECTIVE
Since it is widely recognized that stress influences drug seeking, we decided to investigate whether stress, acute or repeated, could influence the changes in FGF-2 gene expression brought about by cocaine.


RESULTS
Our data demonstrate that stress and cocaine interact to produce significant changes on FGF-2 expression in rat prefrontal cortex and striatum. In prefrontal cortex, our experiments demonstrated that a single exposure to stress potentiated cocaine-induced FGF-2 elevation, whereas prolonged stress prevented the modulation of the trophic factor in response to cocaine. In striatum, the magnitude of cocaine-induced FGF-2 response is enhanced by repeated stress, whereas no interaction was observed when acute stress and single exposure to cocaine were combined.


CONCLUSIONS
Our findings demonstrate that stress interacts with cocaine to alter the pattern of FGF-2 expression in a way that depends on whether stress is acute or chronic and in a regionally selective fashion. These results identify a potential molecular target through which stress alters cellular sensitivity to cocaine and might prove useful in understanding the mechanisms underlying brain vulnerability to stress.
Fumagalli
Fabio
F
Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy.
Di Pasquale
Laura
L
Caffino
Lucia
L
Racagni
Giorgio
G
Riva
Marco Andrea
MA
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological
D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D003042:Cocaine