These data indicate that a history of alcohol drinking by 3xTg-AD mice is associated with diminished PPI of the startle response. At the age tested (7–8 months), saccharin exposed 3xTg-AD mice did not exhibit altered PPI. This suggests that alcohol exacerbated the onset of cognitive dysfunction in the 3xTg-AD mouse model. PPI of the startle response is regulated by interconnected forebrain circuits including the PFC, entorhinal cortex, ganglia, HPC, and AMY (Swerdlow, Geyer, & Braff, 2001). Altered sensory processing is a common feature of AD and is consistent with recent evidence of PPI deficits linked to AD pathology in the lateral entorhinal cortex (LEC) of humans and mouse models (Khan et al., 2014). Indeed, entorhinal cortex lesions are associated with reduced PPI (Goto, Ueki, Iso, & Morita, 2002). However, deficits in PPI also underlie a variety of neuropsychiatric disorders including obsessive-compulsive disorder, schizophrenia, anxiety, and PTSD (Geyer & Swerdlow, 2001; Hoenig, Hochrein, Quednow, Maier, & Wagner, 2005; Kohl, Heekeren, Klosterkotter, & Kuhn, 2013) and may reflect diminished ability to filter or process relevant environmental stimuli. Thus, the alcohol-induced reduction in PPI may reflect the impact of extended alcohol drinking across a continuum of affective and neurological disorders in 3xTg-AD mice.
