A single administration of FGF2 on PND1 increased cocaine

self-administration in adulthood (Turner et al., 2009). This effect is selective as there were no associated differences in spatial or appetitive learning. Moreover, there were no sustained changes in gene expression in the dopaminergic system seen in the adult animal. This does not preclude the possibility that early exposure to FGF2 primed the dopaminergic system, which in turn led to increased drug-taking behavior in adulthood. Whether the actions of early life FGF2 are mediated via dopamine Selleck Pfizer Licensed Compound Library or other mechanisms, the ability of this growth factor to enhance drug-taking behavior identifies it as a molecular antecedent of vulnerability for substance abuse. Given the fact that drugs of abuse interact with stress, it is notable that both stress and drugs of abuse converge to modulate FGF2 expression. Thus, in the prefrontal cortex, acute stress potentiated the cocaine-induced increase in FGF2 expression, whereas prolonged stress prevented the response of FGF2 to cocaine (Fumagalli et al., 2008). In the striatum, the cocaine-induced FGF2 response was only increased following repeated stress. In summary, FGF2 appears to promote both the initial vulnerability and the sequelae of substance abuse. Its administration in early life enhances the propensity for self-administration of drugs KU57788 of abuse in adulthood.

In turn, repeated exposure to drugs of abuse induces FGF2 expression especially in the dopaminergic system, and this induction is required for the development of sensitization. Overall, FGF2, along with FGFR1, can be construed as molecular

factors that modulate emotional reactivity—higher FGF2 levels render animals more prone to novelty and drug taking behavior, while lower FGF2 levels render animals less prone to drug seeking but more prone to anxiety- and depression-like behaviors. Other molecules, such as NCAM, can also interact with the FGF receptors and appear to play a role in the control of emotionality. NCAM polymorphisms have been observed in conjunction with mood disorders 3-mercaptopyruvate sulfurtransferase in humans (Atz et al., 2007; Vawter, 2000). In animal models, NCAM responds to stress system activation, with upregulation of its expression in the cortex following acute corticosterone injections and downregulation following chronic corticosterone (Sandi and Loscertales, 1999)—a pattern that mirrors the regulation of FGF2 by this stress hormone. However, the isoform of NCAM is also important. For example, exposure to a stressful situation decreased NCAM-180 levels in the hippocampus without affecting the levels of NCAM-140 or NCAM-120 (Sandi et al., 2005). Finally, posttranslational modifications of NCAM (polysialylation) can also be affected by stress (Cordero et al., 2005). Similar to FGF2, FGL, a fragment of the NCAM structure (Carafoli et al., 2008; Ditlevsen et al.