Also, as noted above, precipitated withdrawal from chronic nicotine produced anxiogenic-like effects that were blocked by a CRF1 receptor antagonist (George et al., 2007) and increases in reward thresholds that were reversed by a CRF antagonist (Bruijnzeel et al., 2007). Extracellular CRF has been shown to be increased in the amygdala during withdrawal from chronic nicotine (George et al., 2007). From a developmental perspective, increased CRF-like immunoreactivity has been observed in adult rats exposed to nicotine during adolescence and has been linked to an anxiety-like phenotype (Slawecki et al., 2005). Systemic administration of a CRF1 antagonist blocked the increased self-administration of nicotine associated with withdrawal in extended access (23 h) animals (George et al., 2007). These results suggest that CRF in the basal forebrain also may have an important role in the development of the aversive motivational effects that drive the increased drug seeking associated with cocaine, heroin, and nicotine dependence.
