Article

Anhedonic-like traits and lack of affective deficits in 18-month-old C57BL/6 mice: Implications for modeling elderly depression

Lilly Research Labs/Lilly Corporate Center, Delaware St., Indianapolis 839 S, IN 46225 USA.
Experimental gerontology (Impact Factor: 3.49). 05/2012; 47(8):552-64. DOI: 10.1016/j.exger.2012.04.010
Source: PubMed

ABSTRACT

The prevalence of depression increases with aging. We hypothesized that like humans, old animals exhibit anhedonic-like behavior, along with signs of behavioral despair. In rodents, anhedonia, a reduced sensitivity to reward, which is listed as a core feature of major depression in the DSM-IVR, can be measured by a decrease in intake of and preference for sweet solutions. Here, sucrose intake, forced swimming, immobility in the modified tail suspension test, novelty exploration, grooming, anxiety and locomotor activity were compared in naïve 3- and 18-month-old male C57BL/6 mice. The absolute amounts and the ratio of consumed 1% sucrose solution to water intake was significantly smaller in 18-month-old mice than in 3-month-old mice. The consumption of 5%-sucrose solution requiring high levels of drinking effort, novelty exploration in two setups and grooming behavior in the splash test were reduced in older animals. Analysis of other behaviors suggested that the above-mentioned signs of anhedonic-like traits were unlikely to be attributable to the potential effect of aging on metabolic needs for water, taste perception, motor capabilities or the induction of essential anxiety and neophobia. A 4-week treatment with the antidepressant imipramine (7mg/kg/day) or dimebon, a compound with suggested neuroprotective proneurogenic properties (1mg/kg/day) restored sucrose intake and preference in 18-month-old mice. Meanwhile, young and old mice showed no differences in the parameters of behavioral despair evaluated in the forced swim and modified tail suspension tests. Thus, the behavioral profile of aged mice parallels that of humans with elderly depression, in whom the symptoms of hedonic deficits typically outweigh affective disturbances. The assessment of anhedonic-like traits with the sucrose preference test in 18-month-old mice will be useful in preclinical studies of elderly depression.

Download full-text

Full-text

Available from: Julie Vignisse
  • Source
    • "This procedure was carried out twice with a 24 h interval between tests. The latency of the first episode of immobility, the total duration of this behaviour, and mean velocity were scored using Noldus EthoVision XT 8.5 (Noldus Information Technology , Wageningen, Netherlands) according to the protocol that was previously validated [41]. In accordance with the commonly accepted criteria of immobility, the immobility behaviour was defined as the absence of any movements of the animals' head and body. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies.
    Full-text · Article · Jun 2015 · BioMed Research International
  • Source
    • "Papp et al., 1991; Willner et al., 1992; Gronli et al., 2005); its alleviation by anti-depressant drugs (e.g. Muscat et al., 1992; Nestler et al., 2002; Deussing, 2006; McArthur and Borsini, 2006; Malatynska et al., 2012); and its co-variation with other depression-like features including learned helplessness (e.g. Strekalova et al., 2004) and negative cognitive biases (Rygula et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Investigating depression-like conditions in animals is methodologically challenging, but potentially important for welfare. Some riding horses display 'withdrawn' states of inactivity and low responsiveness that resemble the reduced engagement with the environment shown by certain depressed patients. To assess whether these animals are experiencing a depression-like state, we investigated anhedonia - the loss of pleasure, a key symptom of human depression - in 20 withdrawn and non-withdrawn horses from the same stable. The time horses spent being withdrawn appeared unrelated to age or sex, but correlated with time devoted to stereotypic behaviour, a possible marker of lifetime stress. Comparison with data collected 5 years earlier also revealed that horses scored as withdrawn then remained significantly likely to display the behaviour. We measured sucrose intake, a classic measure of anhedonia never previously applied to horses. Flavoured sugar blocks, novel to these subjects, were mounted in each stall and weighed 3, 8, 24 and 30h after provision. We predicted that if affected by depression-like states, the most withdrawn horses would consume the least sucrose. This prediction was met (F1,18=4.65, two tailed p=0.04). This pattern could, however, potentially reflect general appetite levels and/or food neophobia. To control for these confounds, hay consumption was measured over 5 days, as were subjects' latencies to eat a meal scented with a novel odour. Although low hay consumption and long latencies to eat scented food did predict low sucrose consumption, statistically controlling for these confounds did not eliminate the relationship between being withdrawn and consuming less sucrose (although reducing it to a strong trend): F1,15=4.28, two-tailed p=0.056. These data thus suggest long-lasting depression-like states in certain riding horses, which correlate with stereotypic behaviour and are characterised by anhedonia and bouts of 'withdrawn' unresponsiveness.
    Full-text · Article · Jan 2015 · Applied Animal Behaviour Science
  • Source
    • "Emotional states influence food intake, weight gain, metabolism, food preferences, and/or taste preferences in humans, mice, rats, and hamsters12345678. Despite the extent of this phylogenetic conservation, relatively few reports have focused on emotional factors in energy balance [2,91011 . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Anorexia and anxiety cause significant mortality and disability with female biases and frequent comorbidity after puberty, but the scarcity of suitable animal models impedes understanding of their biological underpinnings. It is reported here that in adult or weanling Syrian hamsters, relative to social housing (SH), social separation (SS) induced anorexia characterized as hypophagia, weight loss, reduced adiposity, and hypermetabolism. Following anorexia, SS increased reluctance to feed, and thigmotaxis, in anxiogenic environments. Importantly, anorexia and anxiety were induced post-puberty with female biases. SS also reduced hypothalamic corticotrophin-releasing factor mRNA and serum corticosteroid levels assessed by RT-PCR and RIA, respectively. Consistent with the view that sex differences in adrenal suppression contributed to female biases in anorexia and anxiety by disinhibiting neuroimmune activity, SS elevated hypothalamic interleukin-6 and toll-like receptor 4 mRNA levels. Although corticosteroids were highest during SH, they were within the physiological range and associated with juvenile-like growth of white adipose, bone, and skeletal muscle. These results suggest that hamsters exhibit plasticity in bioenergetic and emotional phenotypes across puberty without an increase in stress responsiveness. Thus, social separation of hamsters provides a model of sex differences in anorexia and anxiety during adulthood and their pathogeneses during adolescence.
    Full-text · Article · May 2014 · Physiology & Behavior
Show more