Two of the most studied cognitive enhancers of extinction learning are DCS and yohimbine, an alpha2-receptor antagonist that promotes norepinephrine release (Kaplan and Moore, 2011). As mentioned previously, DCS has been shown to enhance extinction learning in rats and humans and facilitate exposure therapy in patients with anxiety (Davis et al., 2006; Hofmann, 2007, 2008; Ledgerwood et al., 2003, 2004, 2005; Norberg et al., 2008; Ressler et al., 2004; Walker et al., 2002). Moreover, DCS given immediately after extinction learning prevents recovery of fear (Ledgerwood et al., 2004) and enhances extinction recall in rats, suggesting that DCS also mediates consolidation of extinction memories (Ledgerwood et al., 2003). Likewise, yohimbine also enhances fear extinction in rats and humans (Holmes and Quirk, 2010) and has been shown to facilitate exposure therapy in patients with claustrophobia (Powers et al., 2009). However, there are concerns about the efficacy of these agents over repeated sessions (i.e. with chronic use), which produces behavioral desensitization (Parnas et al., 2005; Storch et al., 2007) and in preventing relapse in translational applications (Kaplan and Moore, 2011).
