Depression-like state behavioural outputs may confer beneficial outcomes in risky environments

Abstract

Recent theories in evolutionary medicine have suggested that behavioural outputs associated with depression-like states (DLS) could be an adaptation to unpredictable and precarious situations. In animal models, DLS are often linked to diverse and unpredictable stressors or adverse experiences. Theoretically, there are a range of potential fitness benefits associated with behavioural inhibition (typical to DLS), as opposed to more active/aggressive responses to adverse or uncontrollable events. This stance of evolutionary medicine has to our knowledge not been tested empirically. Here we address a possible key benefit of behavioural inhibition in a comparative model for social stress (territorial rainbow trout). By treating fish with the fast-acting antidepressant ketamine, we reversed the behavioural inhibition ( i . e . stimulated an increase in activity level) in subordinate fish. During confrontation with a previously unfamiliar larger, aggressive and dominant individual, this increase in activity led to higher amounts of received aggression compared to sham-treated subordinates. This suggests that the behavioural inhibition characterizing animal models of DLS is indeed an effective coping strategy that reduces the risk of injuries in vulnerable social situations.

Behavioral and neurophysiological effects of buspirone in healthy and depression-like state juvenile salmon

“…Furthermore, the DLS-like fish, having experienced prolonged chronic stress compared to the short-term stress experienced by healthy fish in the dose response experiment, may have also resulted in a disparity in responses to buspirone treatment. That is, while the dose response experiment fish were experiencing stress as a response to handling, moving, and a novel environment, the DLS-like fish fit a profile of chronic stress that results in traits such as stunted growth, anorexia from lack of feeding, behavioral inhibition, and listlessness ( Stien et al, 2013 ; Vindas et al, 2016 , 2019 ). Fish under continued stress have also been observed to have altered neuroendocrine responses ( Barton, 2002 ; Tort, 2011 ; Vindas et al, 2019 ) and suffer from impaired cognitive function and an overall decline in physical health that increases their risk of mortality ( Barton et al, 1987 ; Juell, 1995 ).…”

“…That is, while the dose response experiment fish were experiencing stress as a response to handling, moving, and a novel environment, the DLS-like fish fit a profile of chronic stress that results in traits such as stunted growth, anorexia from lack of feeding, behavioral inhibition, and listlessness ( Stien et al, 2013 ; Vindas et al, 2016 , 2019 ). Fish under continued stress have also been observed to have altered neuroendocrine responses ( Barton, 2002 ; Tort, 2011 ; Vindas et al, 2019 ) and suffer from impaired cognitive function and an overall decline in physical health that increases their risk of mortality ( Barton et al, 1987 ; Juell, 1995 ). This experience of prolonged stress is in fact altering their neurophysiology and they may need either stronger doses or a prolonged treatment time to recover behaviorally from the DLS profile.…”

“…This indicates that although these DLS-like fish are able to respond to stress with increased cortisol levels, the magnitude of the response is half that of normal healthy fish. Notably, in the main buspirone experiment all DLS-like fish were essentially granted an environment wherein they had free access to food and no competition or aggression from larger conspecifics (i.e., they were in smaller group of similar-sized fish), both of which are contributing factors to growth disparities and potential emergence of dominance-related disparities between individuals that may lead to DLS profiles ( Cubitt et al, 2008 ; Vindas et al, 2016 , 2019 ). It is therefore possible that we provided an environment in which the DLS-like profile may reverse back to a more normal physiological and behavioral state in both buspirone- and sham-treated fish, which would explain why both these groups showed a healthy 10-fold increase in cortisol to acute stress and similar post-stress 5-HT signaling.…”

Orexin 1 Receptor Antagonism in the Basolateral Amygdala Shifts the Balance From Pro- to Antistress Signaling and Behavior

“…In addition to species-specific anxious behavior and learning, social stress promotes behavioral inhibition, depressed behavioral drive and motivation in some individuals (47), plus a lower rate of adaptive behavior (48). Behavioral depression reveals two distinctive phenotypes related to stress responsiveness in humans and other animals (45,49,50).…”