Selective amotivation deficits following chronic psychosocial stress in mice

Abstract

Amotivation is a major symptom of several psychiatric disorders. However, which specific motivations are most affected in various illnesses is not well understood. In major depressive disorder (MDD), anecdotal evidence suggests the motivation to explore may be especially affected, but direct evidence from either patients or animal models is lacking. To investigate the potential for, and nature of, exploratory drive deficits in MDD, we subjected mice to a chronic social defeat (CSD) manipulation that gives rise to a MDD-like behavioural ensemble, and performed a behavioural battery to examine bodyweight homeostasis, ambulation, anxiety, exploratory behaviour motivated by either novelty or fear, and short-term memory. Consistent with previous reports, we found a disruption of bodyweight homeostasis and reduced ambulation following CSD treatment, but we found no evidence for anxiogenic effects or impairments in short-term memory. Surprisingly, we also observed profoundly delayed and diminished exploration of novel, safe space following CSD, while exploration motivated by fear remained intact. These results extend our knowledge of the behavioural phenotypes in mice resulting from CSD by homing in on specific motivational drives. In MDD patients, reduced exploration could compound disease symptomatology by preventing engagement in what could be rewarding exploration experiences, and targeting deficits in the motivation to explore may represent a novel avenue for treatment.

Dynamic longitudinal behavior in animals exposed to chronic social defeat stress

“…At T2 both SI and NORT exhibited significant deficits in the defeated group, indicated by less time spent in the interaction zone and decreased time spent with the novel object, respectively, compared to the control group ( Fig 1c and 1f ). Similar exploration times in all groups revealed that impairment in the NORTs is not caused by a decline in exploration motivation as has been suggested previously (T1-T3, S4a–S4c Fig [ 14 ]).…”

Repeated social defeat promotes persistent inflammatory changes in splenic myeloid cells; decreased expression of β-arrestin-2 (ARRB2) and increased expression of interleukin-6 (IL-6)

“…It is therefore tempting to speculate that the observed submissive behavior may involve depression and lack of appetite, but also learned helplessness behavior [34] and enhanced punishment avoidance [35,36]. In accordance with earlier observations [1,4,37], we demonstrated a clear stress-induced decrease in weight gain.…”

Using Tandem Behaviour-PET to Examine Dopaminergic Signalling Underlying Exploration

“…The behaviour with the least variation was object interaction (CV = 0.12). All subjects spent more time walking near the walls of the arena than in the centre, as expected, and overall behavioural performance was consistent with other recent investigations [6] [8]. In the subsequent PET scan, regional distribution of 18 F-fallypridebinding potential among a set of regions of interest (ROIs) was consistent with previous studies, exhibiting strongest uptake in regions such as the striatum where D2/D3 receptors are highly expressed, and whole-brain standardised uptake value (SUV) variation (Fig.…”