Digging Signatures in 13-Month-Old 3xTg-AD Mice for Alzheimer's Disease and Its Disruption by Isolation Despite Social Life Since They Were Born

The severity of this pandemic's scenarios will leave significant psychological traces in low resistant and resilient individuals. Increased incidence of depression, anxiety, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder has already been reported. The loss of human lives and the implementation of physical distance measures in the pandemic and post-COVID scenarios may have a greater impact on the elderly, mostly in those with dementia, as OCD and other neuropsychiatric symptoms (NPS) are quite prevalent in this population. Modeling NPS in animals relies in neuroethological perspectives since the response to new situations and traumatic events, critical for survival and adaptation to the environment, is strongly preserved in the phylogeny. In the laboratory, mice dig vigorously in deep bedding to bury food pellets or small objects they may find. This behavior, initially used to screen anxiolytic activity, was later proposed to model better meaningless repetitive and perseverative behaviors characteristic of OCD or autism spectrum disorders. Other authors found that digging can also be understood as part of the expression of the animals' general activity. In the present brief report, we studied the digging ethograms in 13-month-old non-transgenic and 3xTg-AD mice modeling normal aging and advanced Alzheimer's disease (AD), respectively. This genetic model presents AD-like cognitive dysfunction and NPS-like phenotype, with high mortality rates at this age, mostly in males. This allowed us to observe the digging pattern's disruption in a subgroup of 3xTg-AD mice that survived to their cage mates. Two digging paradigms involving different anxiogenic and contextual situations were used to investigate their behavior. The temporal course and intensity of digging were found to increase in those 3xTg-AD mice that had lost their “room partners” despite having lived in social structures since they were born. However, when tested under neophobia conditions, this behavior's incidence was low (delayed), and the temporal pattern was disrupted, suggesting worsening of this NPS-like profile. The outcomes showed that this combined behavioral paradigm unveiled distinct features of digging signatures that can be useful to study these perseverative behaviors and their interplay with anxiety states already present in the AD scenario and their worsening by naturalistic/forced isolation.