STH MULTIDISCIPLINARY INTERNATIONAL
Conference of Biological Psychiatry
«Stress and Behavior»
Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005 Editor: Allan V. Kalueff, PhD
4. EXPERIMENTAL MODELS:
M.A. DERYAGINA MEMORIAL SYMPOSIUM
DISTINCT PHYSIOLOGICAL, BEHAVIORAL AND COGNITIVE FEATURES OF CHRONICALLY STRESSED MICE WITH AND WITHOUT
T. Strekalova, D. Bartsch Central Institute of Metal Health, Mannheim, Germany
Introduction. Anhedonia, a decreased ability to experience pleasures, is a core symptom of human depression. Other important symptoms of depressive disorder are increased basal secretion of glucocorticoids, disturbed circadian activity, elevated percentage of REM sleep and cognitive deficits. One of the most established methods to model anhedonia in rodents is a chronic stress. However, besides anhedonia, chronic stress is known to evoke a number of physiological and behavioral changes. Here, we have established a chronic stress procedure in mice that induces anhedonia only in a subgroup of stressed animals, while another group of stressed animals do not show hedonic deficits and can serve as an internal control for the stress effects not associated with anhedonia.
Methods. We subjected male C57BL/6 mice to a 4-week long chronic stress procedure adopted from a protocol described elsewhere (Strekalova et al., Neuropsychopharmacology, 2004) comprising of a rat exposure, tail suspension and restrained stress. Distinct cohorts of mice from stressed and control groups were studied for their basal glucocorticoid secretion, gene expression, EEG parameters of sleep, circadian activity. Also, animals were investigated for their memory abilities in the step-down avoidance, fear conditioning and Y-maze paradigms at different phases of stress protocol and during anhedonic state.
Results and discussion. Employed stress procedure resulted in a strong decrease of sucrose preference, a measure of anhedonia in rodents. Vulnerability to stress-induced anhedonia was associated with subdominant behavior, as shown by a resident-intruder test. Most animals with dominant behavior did not develop a decrease of sucrose preference. All stressed animals without decrease in 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 in forced swimming and decreased exploration of activity. In contrast, in these paradigms, mice resistant to development of anhedonia, showed behavior, which was very similar to that of non-stressed control group. Both anhedonic and resistant animals exhibited similarly increased parameters of anxiety in elevated O-maze and dark/light box, hyperlocomotion in the open field test and increased aggressive behavior. Anhedonic, but not resistant mice showed elevated levels of basal corticosterone secretion and increased percentage of REM sleep. Anhedonic mice were also found to have specific changes in parameters of circadian rhythm and gene expression profile as compared to resistant and control animals. Anhedonic, but not resistant mice showed impaired learning of hippocampus-dependent memory in contextual fear conditioning, step down avoidance and Y-maze task. In contrast, all groups of mice exhibited normal learning of amygdala-dependent memory in auditory fear conditioning paradigm. Anhedonic and resistant mice, trained in step-down avoidance and Y-maze task during stress phase and scored for memory recall during anhedonic phase, showed normal learning. Both groups of animals, trained before beginning of stress procedure in step-down avoidance and Y-maze task, and
tested for memory recall during stress and anhedonic periods demonstrated normal memory scores, i.e., hedonic deficit did not interfere with recall of previously acquired hippocampus-dependent memory. Together, data on learning and memory in anhedonic mice suggest that anhedonia is selectively associated with impaired acquisition/consolidation of hippocampus-dependent memory.
Conclusion. We conclude that physiological, behavioral and cognitive correlates of stress-induced anhedonia and that of chronic stress are distinct. Therefore, further molecular, neurochemical and electrophysiological studies may be undertaken to address the mechanisms of depressive symptoms using proposed mouse model of depression.