Chronic Mild Stress

A depressive like behavioral state is induced in rodents by exposure to chronic, unpredictable mild stress. This model demonstrates face validity in that exposed animals display signs similar to those of depressed humans, construct validity in that biochemical and cellular changes following CMS resemble similar changes in depressed patients, and predictive validity because the neurobiological and behavioral post CMS changes are effectively reversed by antidepressant drugs. The chronic mild stress procedure has been extensively implemented on both rats and mice.BehavMod3

Reprinted with permission from Macmillan Publishers Ltd:
Neuropsychopharmacology 38(11):2220-2230, copyright 2013

FST=forced swim test, TST=tail suspension test, UCMS=unpredictable chronic mild stress

Cuccurazzu  et al, 2013: Acetyl-L-carnitine, a NF-kB pathway activating pro-neurogenesis compound, reversed CMS induced depressive like behavior. (d)-D- ALC reverses CMS induced increase in immobility in the tail suspension test.(e)- D- ALC not only reverses CMS induced immobility increase in the forced swim test, but actually decrease it compared to control.


Willner P, Towell A, Sampson D, Sophokleous S, Muscat R (1987) Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 93:358-364

Cuccurazzu B, Bortolotto V, Valente MM, Ubezio F, Koverech A, Canonico PL, Grilli M (2013) Upregulation of mglu2 receptors via nf-kappab p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-l-carnitine. Neuropsychopharmacology 38(11):2220-2230