Research reportStrain differences in sucrose preference and in the consequences of unpredictable chronic mild stress
Introduction
In human depression, etiologic factors are numerous and genetic factors can interact with environmental factors to influence the vulnerability to major depression [16]. The accumulation of stressful life events has been reported to be a particularly efficient factor to precipitate the pathology. In view to a better understanding of the phenomena existing in depression, different rodent models have been developed. Among them, the unpredictable chronic mild stress (UCMS) model has been extensively investigated in rats [37]. Rats submitted to chronic exposure to mild stressors show a general decrease in responsiveness to reward, as revealed by decreased palatable sucrose consumption [28]. UCMS has also been found to cause a decrease in the rewarding properties of a variety of natural or drug rewards, as assessed in the place conditioning procedure [29] and an elevation of intracranial self-stimulation reward threshold in the ventral tegmentum [25]. This loss of sensitivity to reward has been compared to anhedonia, one of the core symptoms of human depression (DSM-IV) [1]. Moreover, all these behavioural alterations induced by UCMS can be reversed by chronic antidepressant administration [23], [26], [30], [38]. In this respect, the UCMS model has been claimed to be one of the more relevant animal models of depression [24], [35]. There is an increasing number of studies on UCMS effects in mice and a difference of sensitivity to chronic mild stress has been shown according to the strain of mice, BALB/c and C3H/He strains being more sensitive than C57BL/6 strain [5], [19], [22]. In other test sensitive to antidepressant drugs, a difference in immobility time has been reported between male C57BL/6 and CD1 in the tail suspension test [33], and in the forced swimming test, a strain-dependent effect of UCMS on duration of immobility has recently been shown [5].
In depressed patients, anhedonia may be associated with cognitive disturbances [2], [4], [17], particularly in old patients, which are more sensitive to stressful events [3]. Stress-induced memory impairment has also been found in rodent subjected to spatial tasks [11], [15]. However, the stress used in these studies was rather strong (i.e. uncontrollable foot shocks) and the consequences of UCMS on learning and memory have not been reported.
The aim of the present study was to assess the difference of sensitivity to UCMS on “anhedonia” (sucrose consumption), physical state, body weight, learning and memory in different strains of mice. Past experiments showed that there are differences between strains of mice for sucrose consumption [20]. So in order to conduct the experiment on strains that present a clear-cut sucrose preference in our experimental conditions, we first compared the sucrose consumption in 11 strains of mice and we evaluated their sucrose preference for sucrose solutions of different concentrations.
In the second experiment, mice of the CBA/H, C57BL/6 and DBA/2 strains were chosen according to their high and stable consumption of a palatable sucrose solution and to their ability to learn and memorise a task in a water maze (unpublished results). Using a mouse-adapted version of the UCMS model, mice were submitted to 7 weeks of UCMS. Control animals were housed in a separate room and were only disturbed for behavioural tests. Sucrose consumption, physical state evaluation and body weight measurement were weekly assessed. Indeed, the physical state has been previously shown to be very sensitive to UCMS [7], [22], an effect reversed by chronic treatment with antidepressants [5], [12], [31]. Following a 4 weeks period of UCMS, sub-groups of stressed and non-stressed mice were submitted to a spontaneous alternation test in the Y-maze, and then to the water-maze test for spatial learning and memory.
Section snippets
Animals
Male mice were obtained from the Centre Des Techniques Avancées (Orléans, France). At the start of the experiment, they were singly housed in individual cages () on sawdust bedding. They were maintained under standard laboratory conditions with free access to food and water (12-h-light:12-h-dark cycle, lights on at 07:00 h, T=21±1 °C). Eleven strains of mice (n=5 per strain), 3 months of age at the beginning of experiments, were tested in experiment 1: 129svPas, A/J, C57BL/6J, BS,
Statistical analysis
In experiment 1, since the size of groups was small (i.e. five subjects per group), data of both sucrose consumption and preference were statistically analysed by Kruskal–Wallis tests with the Monte-Carlo estimations. In experiment 2, data of body weight and sucrose consumption (total and per gram of body weight) were analysed by analysis of variances (ANOVAs) for repeated-measures and, in case of a significant effect, by two-tailed Student’s t-test. Data of sucrose preference, showing a no
Sucrose consumption and preference in 11 strains of mice
Basal water and sucrose consumption are illustrated in Table 1. Results show no significant inter-strain difference in water consumption but revealed differences in the intake of sucrose solutions; this strain difference was highly significant whatever the sucrose concentration used. The maximal intake was observed at sucrose concentrations of 8 and 16% in all the strains. For each strain of mice, the sucrose consumption (expressed in gram) was increased with the increasing sucrose
Discussion
The first experiment showed differences in sucrose consumption between the different strains. These differences may result from differences in sucrose appetence, since water intake did not differ between strains. The volume of liquid intake was maximum at sucrose concentrations ranging from 8 to 16%. This confirms previous results obtained in Lister hooded rats [27], showing that sucrose drinking is related to the sucrose solution concentration according to an inverted U-shaped function, with
Acknowledgements
This study was supported by the French Ministère de l’Education Nationale, de la Recherche et de la Technologie, and by the Post-Genome Grant from French Ministère de l’industrie. Authors would like to thanks Sabrina David, Alexandre Herpin and Séverine Grieszmann for their technical help.
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