A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice.

Transgenic Tg2576 mice overexpressing human amyloid precursor protein (hAPP) are a widely used Alzheimer's disease (AD) mouse model to evaluate treatment effects on amyloid beta (Aß) pathology and cognition. Tg2576 mice on a B6;SJL background strain carry a recessive rd1 mutation that leads to early retinal degeneration and visual impairment in homozygous carriers. This can impair performance in behavioral tests that rely on visual cues, and thus, affect study results. Therefore, B6;SJL/Tg2576 mice were systematically backcrossed with 129S6/SvEvTac mice resulting in 129S6/Tg2576 mice that lack the rd1 mutation. 129S6/Tg2576 mice do not develop retinal degeneration but still show Aß accumulation in the brain that is comparable to the original B6;SJL/Tg2576 mouse. However, comprehensive studies on cognitive decline in 129S6/Tg2576 mice are limited. In this study, we used two dementia mouse models on a 129S6 background--scopolamine-treated 129S6/SvEvTac mice (3-5 month-old) and transgenic 129S6/Tg2576 mice (11-13 month-old)-to establish a behavioral test battery for assessing learning and memory. The test battery consisted of five tests to evaluate different aspects of cognitive impairment: a Y-Maze forced alternation task, a novel object recognition test, the Morris water maze, the radial arm water maze, and a Y-maze spontaneous alternation task. We first established this behavioral test battery with the scopolamine-induced dementia model using 129S6/SvEvTac mice and then evaluated 129S6/Tg2576 mice using the same testing protocol. Both models showed distinctive patterns of cognitive impairment. Together, the non-invasive behavioral test battery presented here allows detecting cognitive impairment in scopolamine-treated 129S6/SvEvTac mice and in transgenic 129S6/Tg2576 mice. Due to the modular nature of this test battery, more behavioral tests, e.g. invasive assays to gain additional cognitive information, can easily be added.

Diurnal rodents as an advantageous model for affective disorders: novel data from diurnal degu (Octodon degus).

Circadian rhythms are strongly associated with affective disorders and recent studies have suggested utilization of diurnal rodents as model animal for circadian rhythms-related domains of these disorders. Previous work with the diurnal fat sand rat and Nile grass rat demonstrated that short photoperiod conditions result in behavioral changes including anxiety- and depression-like behavior. The present study examined the effect of manipulating day length on activity rhythms and behavior of the diurnal degu. Animals were housed for 3 weeks under either a short photoperiod (5-h:19-h LD) or a neutral photoperiod (12-h:12-h LD) and then evaluated by sweet solution test and the forced swim test for depression-like behavior, and in the light/dark box and open field for anxiety-like behavior. Results indicate that short photoperiod induced depression-like behavior in the forced swim test and the sweet solution preference test and anxiety-like behavior in the open field compared with animals maintained in a neutral photoperiod. No effects were shown in the light/dark box. Short photoperiod-acclimated degu showed reduced total activity duration and activity was not restricted to the light phase. The present study further supports the utilization of diurnal rodents to model circadian rhythms-related affective change. Beyond the possible diversity in the mechanisms underlying diurnality in different animals, there are now evidences that in three different diurnal species, the fat sand rat, the grass Nile rat and the degu, shortening of photoperiod results in the appearance of anxiety- and depression-like behaviors.

It is darkness and not light: Depression-like behaviors of diurnal unstriped Nile grass rats maintained under a short photoperiod schedule.

Circadian rhythms are strongly implicated in affective disorders and some recent studies suggested that diurnal rodents might be advantageous model animals for them. In line with this possibility, previous work demonstrated that in the diurnal fat sand rat, short photoperiod conditions result in depression- and anxiety-like behavioral phenotype that is relieved with bright light treatment. To further explore the possibility of using diurnal species as model animals for affective disorders, the present study examined the effects of short photoperiod schedule in an additional diurnal rodent, the unstriped Nile grass rat. Results indicate that 6 weeks short photoperiod (5 h light/19 h dark) regimen induced depression-like behavior in the forced swim test and the saccharin preference test compared with animals maintained in a neutral photoperiod regimen (12 h light/12 h dark). No effects were shown in the light/dark box model of anxiety or in a test for spontaneous activity. These results demonstrate that photoperiod manipulations in diurnal rodents induce affective-like behavioral change and support the possibility that diurnal rodents might provide a good potential as model animals for depression spectrum disorders.