Coexistence of Anhedonia and anxiety-independent increased novelty-seeking behavior in the chronic mild stress model of depression
Introduction
Anhedonia, one of the core symptoms of major depression, is defined as “markedly diminish interest or lack of reactivity to pleasurable stimuli” (American Psychiatric and Association, 1994). Preclinical studies, which were targeted at modeling anhedonia, also demonstrated a generalized decrease in sensitivity to reward (to review, see Willner, 2005). For example, chronic mild stress model (CMS), which is a highly validated animal model of depression, resulted in a robust decline of sucrose preference/intake. Besides, CMS abolished or attenuated the conditioned place preference effect induced by sweet solution, palatable food (Papp et al., 1991), low-dose of amphetamine (Papp et al., 1991) and morphine (Valverde et al., 1997). CMS also caused an increase in the threshold current required to support ventral tegmentum self-stimulation (Moreau et al., 1992), and reduced male sexual activity (Grønli et al., 2005). All of the above evidence indicated a decrease in the reward value of a certain reinforcer. In the meantime, a number of studies consistently demonstrated that patients with major depression diagnosis scored significantly higher than healthy subjects on harm avoidance propensity (Abrams et al., 2004, Chien and Dunner, 1996, Celikel et al., 2009, Hansenne et al., 1997, Nery et al., 2009, Tanaka et al., 1998). Since depressed individuals display decreased reward sensitivity and increased harm avoidance tendency, novelty-seeking behavior should be straightly inhibited in depression. Nevertheless, data in this aspect are rather inconsistent or even contradictory. For example, although hospitalized depressed patients scored significantly lower than matched controls on sensation-seeking (Carton et al., 1992, Carton et al., 1995), a propensity to seek out varied, novel and intense sensations which was a driving construct underlying novelty-seeking behavior (Zuckerman, 1994), others demonstrated a significantly higher novelty-seeking score of depressed patients (Nery et al., 2009). In preclinical research, chronic stress-induced anhedonia in mice was reported to associate with reduced exploration to a novel object (Strekalova et al., 2004). In contrast, animals predisposed to learned helplessness with reduced sucrose intake displayed significantly increased exploration to a novel environment which has been interpreted as an increase in novelty-seeking behavior (Shumake et al., 2005). The above results meant that the alterations in novelty-seeking behavior of depressed individuals are by far unclear. This may derive from the dual properties of novelty, which contained both rewarding and aversive components (Glanzer, 1958, Bardo et al., 1996, Bevins and Bardo, 1999, Bevins and Besheer, 2005), and elicited approach and avoidance conflict in organism (Hughes, 1997, Montgomery and Monkman, 1955, Montgomery, 1955, Powell et al., 2004).
The present study aimed to examine the effect of anhedonic state on novelty-seeking behavior. CMS model was employed to induce anhedonia in rats. The approach behavior towards a novel object set in the open-field (OF) was manipulated to measure novelty-seeking behavior. Since the expression of novelty-seeking behavior is suggested to be balanced between the approach and fear/anxiety-facilitated avoidance tendencies (Hughes, 1997, Kazlauckas et al., 2005, Montgomery and Monkman, 1955, Montgomery, 1955, Powell et al., 2004), animals’ anxiety level in elevated plus maze (EPM) and in the central area of the OF, as well as the explorative activity in a relatively milder novel cage were also assessed.
In the present study, only a subgroup of animals displayed decreased sucrose preference, which were categorized as the anhedonic animals. The counterparts of these anhedonic animals who were exposed to the same CMS treatment but without these anhedonic expressions were categorized as stress-resistant ones. All the behavioral analyses were made in anhedonic and stress-resistant animals respectively. This methodology possessed significance in that CMS-induced anhedonic and stress-resistant animals have been evidenced to bear distinct behavioral and neurochemical alterations recently (Bergström et al., 2007, Bergström et al., 2008, Strekalova et al., 2004). Thus, if these two “kinds” of animals were examined in an undistinguished way, it is possible that the effect size would be minimized as with whether anhedonic animals showed altered novelty-seeking behavior.
Section snippets
Animals and housing
Forty-eight male Wistar rats (Vital River Laboratories Inc., Beijing, China), weighing 290 to 340 g at the start of the experiment, were used (Permission No. 199036). Except as described below, animals were housed singly in steel-hanging cages (25 × 22.5 × 30 cm) with food and water ad libitum in a temperature (23 ± 2 °C) and humidity (40–50%) controlled environment. All rats were maintained on a 12-hour light-dark cycle (7:00 light on; 19:00 light off) and all experiments were conducted during the
Changes of sucrose preference following CMS treatment
For the comparisons among stress (n = 33) and control (n = 15) group, two-way ANOVA revealed significant effects of “group” (stress vs control) (F[1, 46] = 5.646, p < 0.05), “time”(F[6,276] = 4.347, p < 0.001), and “group” × “time” interaction (F[6,276] = 2.173, p < 0.05) (Fig. 2a). Simple effect analyses demonstrated a significant decrease of preference score in stress group (F[6, 276] = 9.17, p < 0.001) but not in control group (NS) throughout the CMS treatment. The difference between stress and control group was
Discussion
The main aim of the present study was to investigate the impact of anhedonic state on novelty-seeking behavior. Here, we reported that anhedonic animals expressed significantly increased exploration towards the novel object compared with controls. However, the stress-resistant animals did not. The enhanced novel object exploration of anhedonic rats seemed to be goal-directed. Data for analyzing the novel object exploration (time in and number of entries into novelty-seeking area) was collected
Acknowledgements
This work was supported by National natural science foundation grants (30770722, 30470578), Promotive funding for research excellency of Chinese academy of sciences (O7CX191019), and IPCAS science development fund (O8CX093009) to X.G. Zheng.
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