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.

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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.

By combining behavioural analyses with intrinsic signal optical imaging, we analysed visual performance and visual cortical activity in the albino mouse strain BALB/c, which is increasingly being used as an animal model of neuropsychological disorders. Visual acuity, as measured by a virtual-reality optomotor system, was 0.12 cycles per degree (cyc/deg) in BALB/c mice and 0.39 cyc/deg in pigmented C57BL/6 mice. Surprisingly, BALB/c mice showed reflexive head movements against the direction of the rotating stimulus. Contrast sensitivity was significantly lower in BALB/c mice (45% contrast at 0.064 cyc/deg) than in C57BL/6 mice (6% contrast). In the visual water task, visual acuity was 0.3 cyc/deg in BALB/c mice and 0.59 cyc/deg in C57BL/6 mice. Thus, the visual performance of BALB/c mice was significantly impaired in both behavioural tests - visual acuity was ∼ 0.3 cyc/deg lower than in C57BL/6 mice, and contrast sensitivity was reduced by a factor of ∼ 8. In BALB/c mice, visual cortical maps induced by stimulation of the contralateral eye were normal in both activation strength and retinotopic map quality. In contrast, maps induced by ipsilateral eye stimulation differed significantly between the strains - activity in a region representing 15° to 19° elevation in the visual field was significantly weaker in BALB/c mice than in C57BL/6 mice. Taken together, our observations show that BALB/c mice, like the albino animals of other species, have a significantly lower visual performance than C57BL/6 mice and a modified cortical representation of the ipsilateral eye that may impair stereopsis. Thus, our results caution against disregarding vision as a confounding factor in behavioural tests of neuropsychological disorders.