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