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

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 (7 mg/kg/day) or dimebon, a compound with suggested neuroprotective proneurogenic properties (1 mg/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.

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

“…This observation also confirms, in the MRL-lpr model, the robustness of emotional dysfunction by providing further evidence that such behavioral outcomes are likely a primary manifestation of autoimmunity rather than arising from nonspecific illness or peripheral organ pathology. Finally, MRLlpr mice also display anhedonia, another manifestation of murine depressive-like behavior [91], which is is a lack of response to pleasure or reward and is assessed experimentally in following the loss of the typical preference to drink sweetened fluids [92]. Anhedonia is classically considered as a hallmark diagnostic symptom of depression and, in this report, it correlates significantly with a depression-like phenotype in the forced-swim test.…”

Post-stroke depression and the aging brain

“…To this end, various behavioral tests have been proposed to investigate some of the central aspects of human-like depression in rodents. For example, the forced swim test in which rodends are exposed to water stress and are forced to swim [9, 38] or the tail suspension test (animals are suspended horizontaly by tail for a short period of time) [39, 40] are commonly used as behavioral paradigms that quantify behavioral changes in a stressful situation (behavioral despair). These tests measure the immobility of depressed animals in despair situation and have been pharmacologically validated using antidepressant drugs that are already in human use [41, 42].…”

Altered emotionality, hippocampus-dependent performance and expression of NMDA receptor subunit mRNAs in chronically stressed mice

“…Although it is possible that the different behavioral tests may affect subsequent tests, previously published test batteries with similarly employed paradigms have revealed an absence of any testing effects in C57Bl/6J mice (Malatynska et al, 2012;Strekalova & Steinbusch, 2009Vignisse et al, 2011Vignisse et al, , 2013). Hence, we considered possible interfering effects of multiple behavioral test to be minimal in the current study.…”