**2.2 Animal models in major depressive disorder (MDD)**

Major depressive disorder (MDD) is a common, complex, and heterogeneous mental disorder, characterized by persistent sadness and loss of interest in general activities, affecting about 10% of the population worldwide, and which is caused by multifactorial mechanisms not fully understood yet, characterizing MDD as a disorder with many variations in clinical features among the patients, imposing a consequent high variability in the diagnosis, time course of response and remission [45], which is one of the main reasons justifying the intensive search for animal models and biomarkers, aiming for advances in MDD diagnosis [46]. In addition, these advances could be helpful for a better classification for depressive spectrum, and thereby for improving the treatment [47]. The animal models of depression have been developed based on acute or chronic stress exposure, exogenous administration of glucocorticoids, injuries in brain regions and/or genetic manipulations [48–50]. There is a great variation in the number of protocols that


*All of these models show behavioral and molecular changes that can be associated with SCZ.*

*PPI = prepulse inhibition; PFc = prefrontal cortex; PV = parvalbumin; PDE4B = cAMP-specific 3",5"-cyclic phosphodiesterase 4B; DISC1 = disrupted-in-schizophrenia 1; DOPAC = dihydroxyphenylacetic acid; HVA = homovanillic acid; DA = dopamine; poly I:C = Polyinosinic:polycytidylic acid.*

**63**

**Table 3.**

*Animal Models in Psychiatric Disorder Studies DOI: http://dx.doi.org/10.5772/intechopen.89034*

> ↓ Locomotion; ↑ aggressiveness ↓ Grooming; ↓ response to

↑ Sleep disturbance

↓ Food intake; ↓ growth rate; ↓ Locomotion; ↑ aggressiveness; ↓ Response to rewards

↑ Aggressiveness; ↑ fear conditioning; ↓ locomotion; ↓ food

exploratory activity; ↓ Aggression; ↓ sexual

↑ Anhedonia; ↑ sleep disturbance ; ↓ Growth rate

↑ Anxiety-like behavior; ↑ Depression-like behavior; ↑ Novelty responsivity

↑ Locomotion; ↓ working memory; ↓ response to rewards; ↓ food intake; ↑ sleep disturbance; ↑ responsivity to stressors

immobility in forced swim test; ↑ social avoidance; ↑ freezing to context

↓ Activity in enclosed

↑ immobility in forced

↓ sucrose intake under

arena;

stress

*cortex; HPA = hypothalamic–pituitary–adrenal axis.*

swim test;

intake

behavior;

Social defeat ↓ Locomotion; ↓

rewards

models, see also [51] (**Table 3**).

**Stress-induced models**

Learned Helplessness

Unpredictable chronic mild stress

Chronic restraint stress model

Early life stress model

**Brain lesion model**

**Selective inbreeding**

Flinders Sensitive Line rat

Wistar-Kyoto ↓ Locomotion; ↑

Olfactory bulbectomy

can be used to induce these changes, in which the stressor, time of exposure to the stimulus, and other parameters may vary. For more detailed review of MDD

**Model Endophenotype Molecular alterations References**

↓ Norepinephrine ; ↑ BDNF; aberrant miRNA brain- region

↑ Corticosterone; ↓ glucocorticoid

↑ CA3 dendritic atrophy and damage; ↓ neurogenesis in dentate gyrus; ↑ apoptotic cell death;

↓ Volume and cell proliferation in hippocampus and PFc; ↑ corticosteroid; ↓ serotonin;

↑ BDNF expression PFC and

Dysfucntion in HPA and neuro-immune axis;

↓ Serotonin synthesis;

noradrenergic systems

*BDNF = brain-derived neurotrophic factor; miRNA = microRNA; ATP = adenosine triphosphate; PFc = prefrontal* 

*Examples of models for MDD induced by stressors, injuries in brain regions, and by selective inbreeding.*

dysfunction in dopaminergic and

↓ neurotransmitters; ↑ neuronal degeneration; ↑ BDNF; ↓ neuropeptides

↑ Adrenal glands; ↑ corticosterone [72, 73]

[52–57]

[58–61]

[62–64]

[65–67]

[68, 69]

[70, 71]

[74–77]

specific expression

receptor expression; ↓ endogenous ATP

↑ corticosteroid

↓ BDNF

hippocampus

**Table 2.**

*Some examples of SCZ models induced by drugs, genetic manipulation, and prenatal insults.*
