Dynamic modulation of basic Fibroblast Growth Factor (FGF-2) expression in the rat brain following repeated exposure to cocaine during adolescence.
BACKGROUND
Our study stems from four related lines of evidence: (1) FGF-2 is expressed in the developing brain; (2) psychostimulants modulate FGF-2 expression; (3) stress alters FGF-2 expression; and (4) exogenous administration of FGF-2 long-lastingly alters cocaine acquisition of self-administration.


OBJECTIVE
This research aims to study the effects of adolescent cocaine exposure on FGF-2 mRNA levels and its influence on the response to stress.


METHODS
Rats were treated subcutaneously with saline or cocaine from postnatal day (PND) 28 to PND 42, a period that roughly approximates adolescence in humans. At PND 45 and PND 90, rats were exposed to an acute stress. Real-time PCRs were performed on total RNA extracted from the prefrontal cortex, hippocampus, nucleus accumbens and striatum.


RESULTS
In the prefrontal cortex, repeated cocaine treatment during adolescence increased FGF-2 mRNA levels in PND 90 rats and altered its response to an acute stress in both PND 45 and PND 90 rats. In the hippocampus of PND 45 rats, we found an increase of FGF-2 mRNA levels following repeated cocaine administration. No changes in the trophic factor gene expression were found in the striatum and nucleus accumbens.


CONCLUSIONS
Our data show that cocaine exposure during adolescence alters FGF-2 mRNA levels throughout life in rat prefrontal cortex and modulates its response to an adverse event. These results point to FGF-2 as a potential molecular target through which exposure to cocaine early in life may dynamically and persistently alter brain homeostasis.
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, Milan, Italy.
Giuseppe
G
Giannotti
Lucia
L
Caffino
Francesca
F
Calabrese
Giorgio
G
Racagni
Fabio
F
Fumagalli
D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000523:psychology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013315:Stress, Psychological / Q000378:metabolism*
D016222:Fibroblast Growth Factor 2; D003042:Cocaine