Exploring the similarities between risk factors triggering depression in humans and elevated in-cage "inactive but awake" behavior in laboratory mice.

Introduction: Depression is a human mental disorder that can also be inferred in non-human animals. This study explored whether time spent inactive but awake ("IBA") in the home-cage in mice was further triggered by risk factors similar to those increasing vulnerability to depression in humans (early life stress, genetic predispositions, adulthood stress). Methods: Eighteen DBA/2 J and 18 C57BL/6 J females were tested, of which half underwent as pups a daily maternal separation on post-natal days 2-14 (early-life stress "ELS") (other half left undisturbed). To assess the effect of the procedure, the time the dams from which the 18 subjects were born spent active in the nest (proxy for maternal behavior) was recorded on post-natal days 2, 6, 10 and 14 for 1 h before separation and following reunion (matched times for controls), using live instantaneous scan sampling (total: 96 scans/dam). For each ELS condition, about half of the pups were housed post-weaning (i.e., from 27 days old on average) in either barren (triggering IBA and depression-like symptoms) or larger, highly enriched cages (n = 4-5 per group). Time mice spent IBA post-weaning was observed blind to ELS treatment using live instantaneous scan sampling in two daily 90-min blocks, two days/week, for 6 weeks (total: 192 scans/mouse). Data were analyzed in R using generalized linear mixed models. Results: The dams were significantly more active in the nest over time (p = 0.016), however with no significant difference between strains (p = 0.18), ELS conditions (p = 0.20) and before/after separation (p = 0.83). As predicted, post-weaning barren cages triggered significantly more time spent IBA in mice than enriched cages (p < 0.0001). However, neither ELS (p = 0.4) nor strain (p = 0.84) significantly influenced time mice spent IBA, with no significant interaction with environmental condition (ELS × environment: p = 0.2861; strain × environment: p = 0.5713). Discussion: Our results therefore only partly support the hypothesis that greater time spent IBA in mice is triggered by risk factors for human depression. We discuss possible explanations for this and further research directions.

Do greater levels of in-cage waking inactivity in laboratory mice reflect a spontaneous depression-like symptom? A pharmacological investigation.

We previously identified in laboratory mice an inactive state [being awake with eyes open motionless within the home cage; inactive but awake, 'IBA'] sharing etiological factors and symptoms with human clinical depression. We further test the hypothesis that greater time spent displaying IBA indicates a depression-like state in mice by investigating whether the antidepressant Venlafaxine, environmental enrichment, and their combination, alleviate IBA. Seventy-two C57BL/6J and 72 DBA/2J female mice were pseudo-randomly housed post-weaning in mixed strain-pairs in non-enriched (NE; 48 pairs) or in environmentally enriched (EE; 24 pairs) cages. After 34 days, half of the mice housed in NE cages were either relocated to EE cages or left in NE cages. For each of these conditions, half of the mice drank either a placebo or the antidepressant Venlafaxine (10 mg/kg). The 48 mice housed in EE cages were all relocated to NE cages and allocated to either the placebo (n = 24) or Venlafaxine (n = 24). IBA data were collected prior to and after environmental adjustment by trained observers blind to the pharmacological and environmental adjustment treatments. Data were analyzed using GLM models. NE cages triggered more IBA than EE cages (Likelihood-Ratio-Test Chi23 = 53.501, p < 0.0001). Venlafaxine and environmental enrichment appeared equally effective at reducing IBA (LRT Chi23 = 18.262, p < 0.001), and combining these approaches did not magnify their effects. Enrichment removal triggered IBA increase (LRT Chi21 = 23.050, p < 0.001), but Venlafaxine did not overcome the increase in IBA resulting from enrichment loss (LTR Chi21 = 0.081, p = 0.775). Theoretical implications for putative depression-like states in mice, and further research directions, are discussed.

Could Greater Time Spent Displaying Waking Inactivity in the Home Environment Be a Marker for a Depression-Like State in the Domestic Dog?

Dogs exposed to aversive events can become inactive and unresponsive and are commonly referred to as being "depressed", but this association remains to be tested. We investigated whether shelter dogs spending greater time inactive "awake but motionless" (ABM) in their home-pen show anhedonia (the core reduction of pleasure reported in depression), as tested by reduced interest in, and consumption of, palatable food (KongTM test). We also explored whether dogs being qualitatively perceived by experts as disinterested in the food would spend greater time ABM (experts blind to actual inactivity levels). Following sample size estimations and qualitative behaviour analysis (n = 14 pilot dogs), forty-three dogs (6 shelters, 22F:21M) were included in the main study. Dogs relinquished by their owners spent more time ABM than strays or legal cases (F = 8.09, p = 0.032). One significant positive association was found between the KongTM measure for average length of KongTM bout and ABM, when length of stay in the shelter was accounted for as a confounder (F = 3.66, p = 0.035). Time spent ABM also correlated with scores for "depressed" and "bored" in the qualitative results, indirectly suggesting that experts associate greater waking inactivity with negative emotional states. The hypothesis that ABM reflects a depression-like syndrome is not supported; we discuss how results might tentatively support a "boredom-like" state and further research directions.