Animal models of major depression: drawbacks and challenges

Abstract

Major depression is a leading contributor to the global burden of disease. This situation is mainly related to the chronicity and/or recurrence of the disorder, and to poor response to antidepressant therapy. Progress in this area requires valid animal models. Current models are based either on manipulating the environment to which rodents are exposed (during the developmental period or adulthood) or biological underpinnings (i.e. gene deletion or overexpression of candidate genes, targeted lesions of brain areas, optogenetic control of specific neuronal populations, etc.). These manipulations can alter specific behavioural and biological outcomes that can be related to different symptomatic and pathophysiological dimensions of major depression. However, animal models of major depression display substantial shortcomings that contribute to the lack of innovative pharmacological approaches in recent decades and which hamper our capabilities to investigate treatment-resistant depression. Here, we discuss the validity of these models, review putative models of treatment-resistant depression, major depression subtypes and recurrent depression. Furthermore, we identify future challenges regarding new paradigms such as those proposing dimensional rather than categorical approaches to depression.

Evidence for an apathy phenotype in aged mice

“…In the novelty supressed feeding test, aged mice were quicker to consume food in a novel environment suggested lower novelty-induced hyponeophagia. These findings are consistent with reduced anxiety and opposite to the effects seen in rodent models of depression where increased feeding latencies are consistently observed (Planchez et al, 2019). In contrast, aged animals had reduced reward sensitivity in the SPT.…”

“…Using a series of different measures of stress reactivity and affective behaviour we also found evidence of a blunted emotional response in aged mice. It is interesting to observe that the effects were not typical of that seen in models of depression (Planchez et al, 2019). In assays used to measure anxiety and depression-related behaviours we found effects suggesting lower levels of anxiety but reduced reward sensitivity.…”

Prenatal psychosocial stress-induced behavioral and neuroendocrine abnormalities are associated with sex-specific alterations in synaptic transmission and differentially modulated by maternal environment

“…No differences were observed across groups in the total number of immobility episodes ( Figure 2E; F1,25= 2.91, P=0.1006 for PS effect; F1,25= 0.91, P=0.3487 for CF effect). We used the sucrose preference test (SPT) to evaluate anhedonia, a symptom often seen in depression (Planchez et al, 2019). A significant PS x CF interaction was observed on the preference for 4% sucrose solution ( Figure 2F; F1,26.9= 3.24, p=0.0416).…”

New Developments in Behavioral Pharmacology

“…In this study, it was identified that at 3-week post-ovariectomy appears anxietylike behavior, but from 6-week post-ovariectomy in addition to anxiety-like behavior, also increases depression-like behavior in rats, supporting an experimental model of surgical post-menopause [25] measured by scoring ambulation, rearing or nose approaching to an object; sexual behavior can be measured by conditioned place preference, number of mounts, latency and number of ejaculations. All these behaviors are normally studied under controlled environments that are designed specifically to the required behavioral display and every feature of the environment; the experimental subjects or chemical agents with probed effects on humans have been studied in this environment with the purpose of establishing these manipulations as models of a specific behavior (see Table 2) as spatial learning and memory, or models of specific pathologies behaviorally expressed as is the case of anxiety [28], depression [29], obsessive compulsive disorder [30], Parkinson [31], epilepsy [32] or addictive behaviors [33], and sleep deprivation [34], among others.…”