Requirement of endogenous basic fibroblast growth factor for sensitizationto amphetamine

Repeated exposure to amphetamine produces long-lasting increases in sensiti vity to its effects. We reported previously that repeated amphetamine treat ment results in increased astrocytic expression of basic fibroblast growth factor (bFGF) in the ventral tegmental area (VTA) and substantia nigra comp acta (SNc) and that this effect is prevented by coadministration of a nonsp ecific glutamate receptor antagonist. Here we show that the development of sensitization to amphetamine is prevented when amphetamine injections are p receded by infusions of a neutralizing antibody to bFGF into the VTA. In ad dition, we show that astrocytic bFGF expression is increased in the VTA and SNc of animals that exhibit behavioral sensitization and that the number o f bFGF-immunoreactive astrocytes in these regions is strongly and positivel y correlated with the magnitude of sensitization. Cotreatment with an NMDA glutamate receptor antagonist blocks both the development of behavioral sen sitization and bFGF induction. These results show that endogenous bFGF is n ecessary for the development of sensitization to amphetamine and suggest th at bFGF mediates the glutamatergic-dopaminergic interaction that initiates the long-term consequences of repeated drug use.