Rodent Model of Depression
Rodents pre-exposed to an inescapable (uncontrollable) aversive stimulus – such as a foot shock – in a specific context display deficient learning behavior relative to controls when the same stimulus is applied in the same context in a subsequent two-way escape-avoidance task. This is the (discrete) learned helplessness effect that can be used in animal models of depression to study the etiology, neurobiology and neuropharmacology of uncontrollability of aversive events.
Learned Helplessness experiments are performed with the Multi Conditioning System “2-compartment paradigms” software using the multi-purpose Active Avoidance arena. Equip the arena with a tunnel gate or a “crawl-through” divider or use a special arena optimized for wired animals in optogenetics or fiber photometry experiments. Administer foot shock only or use light, sound and/or noise to signal the aversive event. In the Active Avoidance & Escape session, a variety of experimental parameters can be customized such as the “safe” area of the arena or the number of transfers for an escape to modify task difficulty. The use of a triadic design (escapable shock, “yoked”-inescapable shock, control) allows examining the influence of uncontrollability per se on the learned helplessness phenotype because both escape and yoked subjects are exposed to the identical amount, intensity, pattern and duration of foot shock. This is done by using a template from a previous escapable session – a feature that is only available in the Multi Conditioning System.
Animal position and movement are continuously detected with high spatial and temporal resolution via 3-dimensional light beam sensors. The system not only discriminates between left and right compartment, it also allows a comprehensive fine evaluation of animal behavior: rearing and jumping events as a measure of emotionality, response latency to and decreased motor activity during foot shock as a measure of motivation and the trial-by-trial learning curve during the escape test as a measure of cognition.
The TTL output signals that are an integral part of the Multi Conditioning System can be used to control 3rd party instruments, e.g. activate optogenetics laser generators depending on the position of the animal in the arena. Please contact us for details!
Ineichen C, Greter A, Baer M, Sigrist H, Sautter E, Sych Y, Helmchen F, Pryce CR. Basomedial amygdala activity in mice reflects specific and general aversion uncontrollability. Eur J Neurosci. 2020 Dec 18. Epub ahead of print.
Kim JY, Yang SH, Kwon J, Lee HW, Kim H. Mice subjected to uncontrollable electric shocks show depression-like behaviors irrespective of their state of helplessness. Behav Brain Res 2017; 322 (Pt A):138-44.
Bergamini G, Sigrist H, Ferger B, Singewald N, Seifritz E, Pryce CR. Depletion of nucleus accumbens dopamine leads to impaired reward and aversion processing in mice: Relevance to motivation pathologies. Neuropharmacology 2016; 109: 306