As noted above, CRF in parts of the extended amygdala is involved in the aversive stimulus effects of opioid withdrawal. The selective CRF1 antagonist antalarmin blocked the place aversion produced by naloxone in morphine-dependent rats (Stinus et al., 2005). CRF1 knockout mice failed to show conditioned place aversion to opioid withdrawal and failed to show an opioid-induced increase in dynorphin mRNA in the nucleus accumbens (Contarino and Papaleo, 2005). CRF1 antagonists also selectively blocked the increase in heroin self-administration observed in heroin-dependent rats with extended access (Greenwell et al., 2008a).
