DEPRESSION

One relatively simplistic and widely used model of depression is the forced-swimming paradigm originally adopted by Porsolt et al. (1978). Naïve rats and mice forced to swim in an aversive and confined environment innately fight to escape the apparatus. Following failed attempts to escape, they become immobile (i.e. float), a behavior generally considered as despair, “depressive-like” behavior. Prior treatment with antidepressants decreases the time spent immobile and increases the latency to reach the first immobility episode.

The tail-suspension test was developed as an alternative to the Forced Swimming test, yet the concept remains the same. Rodents, suspended by their tail, innately attempt to escape from this aversive situation. However, following failed attempts to escape, they experience despair and become immobile. The magnitude of immobility is considered to be correlated with the depressive-like state of the subjects and is significantly decreased by antidepressants.

Learned helplessness, developed in the 1970s by Seligman, refers to the behavioral consequences of repeated exposures to stressful events over which the organism has no control. Learned helplessness is a laboratory phenomenon observed when animals are exposed to incontrollable trauma induced by inescapable footshock and was initially presented as a model of depression. The relationship between depression and anxiety in the learned helplessness model is that anxiety resulting from feelings of loss of control underlies depression. This anxious paradigm has profound and long-lasting disruptive effects on the ability of the animals to learn to escape shocks in another situation such as the two-way avoidance task, in which subjects can escape the light-signaled electrical shock by changing of compartment. Escape deficit, induced by previous inescapable shock session, can be prevented by administering antidepressants.

In the chronic mild unpredictable stress paradigm, animals are subject to a variety of different stressors, including changes in housing condition, physical restraint, forced swimming or water deprivation. With time, this stressful experience experiences lead to various behavioral changes such as anhedonia in the sucrose preference test (reduced intake of a sweetened solution, innately preferred over water), depression-like performance on models of despair and increased anxiety-like behaviors. These depressive effects are reversed by chronic administration of antidepressants.

The differential reinforcement of low-rate 72 seconds (DRL-72 s) task is an operant procedure in which a subject is required to keep pressing a lever for at least 72 seconds in order to obtain a reward. If a response is emitted before the 72 s elapsed, the time counter is reset to 0. This schedule of reinforcement generates low rates of lever-pressing, and a low frequency of reinforced responses. The typical effect of antidepressants is to increase time elapsed between responses, leading to an increase in the frequency of reinforced responses.

The social interaction test by pairs provides a popular and standard paradigm to study general social behavior. This test consists in allowing the experimental subject freely exploring an unfamiliar congener in its homecage or in a neutral environment. Social exploration is measured by the time spent by the experimental subject around the congener as well as the amount and duration of behaviors that compose social interaction (e.g. sniffing, following, allogrooming, biting, mounting, wrestling…). Social avoidance behavior is used in a wide variety of models, for instance for assessing neophobia anxiety and depression-like behaviors.