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Tatyana Strekalova"Behavioral correlates of stress-induced anhedonia in mice"

Abstract :


Anhedonia, a decreased ability to experience pleasures, is a core symptom of human depression, which can be also induced in animals, including mice.
One of the most established methods to evoke anhedonia in rodents is a chronic stress. However, besides anhedonia, chronic stress is known to alter a number of physiological and behavioral variables that is not necessarly related to a depressive-like state. In order to investigate behavioral correlates of the anhedonic status selectevely, we have established a new chronic stress procedure in mice that induces anhedonia only in a subgroup of stressed animals, while the rest of them does not show hedonic deficits and can serve as an internal control for the stress effects not associated with anhedonia.
We subjected male C57BL/6 mice to a 4-week long chronic stress procedure, comprising of a rat exposure, tail suspension and restrained stress. This procedure resulted in a strong decrease of sucrose preference, a measure of anhedonia in rodents. Interestingly, vulnerability to stress-induced anhedonia was associated with subdominant features of social behavior, as shown by a resident-intruder test. All stressed animals without decrease of sucrose preference were regarded as resistant to stress-induced anhedonia and were used as an internal control for the effects of chronic stress alone. Behavioral analysis performed after terminating the stress procedure demonstrated that anhedonia is associated with key analogues of depressive symptoms, such as increased floating during forced swimming, decreased exploration activity and increased immobilization in the tail suspension test. In contrast, in new object exploration paradigm, novel cage, forced swim and tail suspension tests, mice resistant to astress-induced anhedonia showed behavior, similar to that of non-stressed control group. Both stressed mice with and without anhedonia showed similarly increased parameters of anxiety in the elevated O-maze and the dark/light box paradigms, hyperlocomotion in the open field test and loss of body weight. Thus, behavioral correlates of stress-induced anhedonia and that of chronic stress can be separated in proposed model of depression.

Chronic administration of citalopram (15 mg/kg, i.p.), which was started 1 week before stress and continued during the entire period of four-week stress, significantly decreased percentage of anhedonic mice estimated by the end of the chronic stress. Administration of the same dose of citalopram with drinking water, which begun after anhedonia has been induced, restored preference to sucrose in the animals with hedonic deficit after four weeks of treatment. This establishes our paradigm of stress-induced anhedonia as a pharmacologically validated model of depression.

Selected publications

Strekalova T, Gorenkova N, Schunk E, Dolgov O, Bartsch D.
Selective effects of citalopram in a mouse model of stress-induced anhedonia with a control for chronic stress.
Behav Pharmacol. 2006 May;17(3):271-87.
Strekalova T, Spanagel R, Dolgov O, Bartsch D.
Abstract Stress-induced hyperlocomotion as a confounding factor in anxiety and depression models in mice.
Behav Pharmacol. 2005 May;16(3):171-80.

Giovanni Marsicano