The Journal of Neuroscience, 2000, 20:RC55:1-5
RAPID COMMUNICATION
Requirement of Endogenous Basic Fibroblast Growth Factor for
Sensitization to Amphetamine
Cecilia
Flores,
Anne-Noël
Samaha, and
Jane
Stewart
Center for Studies in Behavioral Neurobiology Department of
Psychology, Concordia University, Montreal, Quebec H3G 1M8, Canada
Repeated exposure to amphetamine produces long-lasting increases in
sensitivity to its effects. We reported previously that repeated
amphetamine treatment results in increased astrocytic expression of
basic fibroblast growth factor (bFGF) in the ventral tegmental area
(VTA) and substantia nigra compacta (SNc) and that this effect is
prevented by coadministration of a nonspecific glutamate receptor
antagonist. Here we show that the development of sensitization to
amphetamine is prevented when amphetamine injections are preceded by
infusions of a neutralizing antibody to bFGF into the VTA. In addition,
we show that astrocytic bFGF expression is increased in the VTA and SNc
of animals that exhibit behavioral sensitization and that the number of
bFGF-immunoreactive astrocytes in these regions is strongly and
positively correlated with the magnitude of sensitization. Cotreatment
with an NMDA glutamate receptor antagonist blocks both the development
of behavioral sensitization and bFGF induction. These results show that
endogenous bFGF is necessary for the development of sensitization to
amphetamine and suggest that bFGF mediates the
glutamatergic-dopaminergic interaction that initiates the long-term
consequences of repeated drug use.
Key words:
basic fibroblast growth factor; bFGF; FGF-2; neurotrophic
factors; amphetamine; sensitization; dopamine; glutamate; NMDA
Copyright © 2000 Society for Neuroscience 0270-6474/00/$05.00/0