Several studies have assessed cued and contextual fear conditioning in 6-month-old 3xTg-AD mice as measures of emotional and cognitive processing; however, results are inconsistent. One study reported increased freezing behavior by 3xTg-AD mice when exposed to a context previously paired with shock (Espana et al., 2010), which suggests intact associative memory with enhanced fear response. By contrast, another study reported reduced latency by 3xTg-AD mice to voluntarily enter a context previously paired with shock (Billings et al., 2005), which is consistent with reduced fear or emotional response and may reflect a hippocampal-dependent deficit in spatial memory. Alternatively, some studies have reported no difference between 3xTg-AD mice and WT controls on measures of cued or contextual fear conditioning (Chu, Giannopoulos, Ceballos-Diaz, Golde, & Pratico, 2012; Stover, Campbell, Van Winssen, & Brown, 2015a). In general, however, both the APP and 3xTg-AD mouse models of AD show associative memory deficits and emotional dysfunction (Billings et al., 2005; Gimenez-Llort et al., 2007; Saura et al., 2005) that are associated with Aβ pathology.
