2.3.1. Neuropsychiatric-Like Behaviors

Changes in emotionality increased neophobia, and other signs of anxiety-like responses, all of them BPSD-like behaviors modeled in 3xTg-AD mice [10], were measured in classical unconditioned tests. The test evaluates locomotion/exploration, anxiety-like behaviors, and emotionality under three different anxiogenic conditions: mild neophobia in a new home-cage (corner test), direct exposure to an illuminated field (open-field test), a choice between a dark and a lit chamber (dark–light box test), black corridors of a maze resembling burrows (T-maze test), and interaction with small objects (marble burying test).

### 2.3.2. Corner Test (CT) and Open-Field Test (OF)

Neophobia was assessed in the corner test for 30 s. Animals were individually placed in the center of a clean standard home cage, filled with wood save bedding. The number of corners visited were recorded during 30 s [26]. Latency to realize the first rearing and the number of rearings were also registered [10]. Immediately after the CT, mice were placed in the center of an open field (metalwork, white box, 42 × <sup>38</sup> × 15 cm3) and observed for 5 min [27]. The ethogram, described by the temporal profile of the following sequence of behavioral events, was recorded: duration of freezing behavior, latency to leave the central square, and that of entering the peripheral ring and latency and total duration of self-grooming behavior. Horizontal (crossings of 10 × 10 cm2 squares) and vertical (rearings with wall support) locomotor activities were also measured. During the tests, defecation boli and urination were also recorded. The repeated test, 24 h later, was used to evaluate the long-term memory of these experiences [28].

### 2.3.3. Dark–Light Box Test (DLB)

Anxiety and risk assessment were measured for 5 min after introducing the animals into the dark compartment of the DLB (Panlab, S.L., Barcelona, Spain). The apparatus consisted of two compartments (black, 27 × <sup>18</sup> × 27 cm3, white, 27 × <sup>27</sup> × 27 cm<sup>3</sup> illuminated by a red 20 W bulb) connected by an opening (7 × 7 cm3). The experimental room was kept in darkness (without illumination). Latency to enter, time spent, and the number of entries into the lit compartment were recorded. The number of stretch attendances and self-grooming were also recorded.
