The role of neurotrophic factors in psychostimulant-induced behavioral and neuronal plasticity.

Several neurotrophic factors influence the development, maintenance and survival of dopaminergic neurons in the mammalian central nervous system (CNS), including neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) and glial derived neurotrophic factor (GDNF). This review focuses on the role of these neurotrophic factors in psychostimulant-induced behavioral sensitization, a form of dopamine-mediated neuronal plasticity that models aspects of paranoid schizophrenia as well as drug craving among psychostimulant addicts. Whereas NT-3, CNTF and bFGF appear to play a positive role in psychostimulant-induced behavioral sensitization, GDNF inhibits this form of behavioral plasticity. The role of BDNF in behavioral sensitization, however, remains elusive. While it has been shown that neurotrophic factors can influence the behavioral, structural and biochemical phenomena related to psychostimulant-induced neuronal plasticity, it is unclear which neurotrophic factors are important physiologically and which have purely pharmacological effects. In either case, examining the role of neurotrophic factors in behavioral sensitization may enhance our understanding of the mechanisms underlying the development of paranoid psychosis and drug craving and lead to the development of novel pharmacological treatments for these disorders.