A more effective way to eliminate unwanted fears would be to erase the fear memory itself. It has long been appreciated that new memories undergo a period of
consolidation in which they are labile and sensitive to disruption (McGaugh, 2000). Long-term synaptic plasticity in the brain requires de novo protein synthesis (Deadwyler et al., 1987, Krug et al., 1984 and Stanton and Sarvey, 1984), and administration of protein synthesis inhibitors soon after learning produces memory impairments (Agranoff et al., 1965, Agranoff and Klinger, 1964 and Davis and Squire, 1984). Therefore, one strategy for reducing pathological fear would be to prevent the consolidation of long-term fear memories soon after a traumatic experience. Consistent with this aim, several www.selleckchem.com/products/pifithrin-alpha.html www.selleckchem.com/products/CP-673451.html investigators have now shown that fear memory is inhibited by systemic posttraining protein synthesis inhibition (Bourtchouladze et al., 1998 and Lattal and Abel, 2001). Moreover, infusion of the protein synthesis inhibitor anisomycin into the BLA within hours of fear conditioning disrupts the consolidation of long-term fear memories and reduces conditional fear responses (Maren et al., 2003, Parsons et al., 2006, Schafe and LeDoux, 2000 and Schafe et al., 1999). In addition to protein synthesis inhibitors, administering behavioral interventions soon after fear conditioning might also disrupt long-term
fear memory by interfering with consolidation processes. For example, it has been reported that administering low-frequency stimulation soon after fear conditioning isothipendyl eliminates conditioning-related changes in MAPK phosphorylation in the BLA, a biochemical correlate of long-term synaptic plasticity and fear memory, as well as fear
memory (Lin et al., 2003a). Based on this evidence, Davis and colleagues explored whether administering extinction trials soon after fear conditioning would yield a permanent loss of fear, rather than the temporary inhibition of fear typically observed with delayed extinction training (Myers et al., 2006). To test this, they administered extinction trials shortly (i.e., 10 min) after fear-potentiated startle conditioning in rats and examined whether fear suppression was more durable than that produced by extinction 24 hr after conditioning. They found that this immediate extinction procedure resulted in a loss of fear that was quite durable and exhibited little spontaneous recovery, reinstatement, or renewal. The implication of these findings is that early extinction training resulted in a permanent fear loss, which is not typical when extinction training is conducted 1 day after conditioning. The lack of fear recovery in this report suggested that immediate extinction might disrupt the consolidation of fear memory, yielding a relatively permanent loss of fear. Although promising, several laboratories have now found that immediate extinction does not always reduce the recovery of fear (Archbold et al., 2010 and Huff et al.