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

in Experimental Gerontology (2012), 47(8), 552-64

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 ... [more ▼]

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 naive 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. [less ▲]

Dimebon Enhances Hippocampus-Dependent Learning in Mouse Models of Appetitive Y-Maze and Inhibitory Step-Down Memory Tasks in Mice

Poster (2011, February 23)

Dimebon, a compound recently proposed for a treatment of Alzheimer’s disorder, was suggested to have memory enhancing properties in pre-clinical and clinical studies. We investigated whether dimebon at ... [more ▼]

Dimebon, a compound recently proposed for a treatment of Alzheimer’s disorder, was suggested to have memory enhancing properties in pre-clinical and clinical studies. We investigated whether dimebon at doses acutely (0.1 mg/kg and 0.5 mg/kg) or repeatedly (0.1 mg/kg) administered to mice via i.p. injections, increases memory scores respectively in an appetitive and an inhibitory learning task. Acute treatment with dimebon at the dose 0.1 mg/kg did not affect learning scores in 3-month-old C57BL/6N. Acute treatment with higher dose of dimebon (0.5mg/kg) was found to enhance inhibitory learning in 3-month-old mice as shown in the step-down avoidance paradigm in C57BL/6N mice. In a model of appetitive learning, a spatial version of the Y-maze, repeated treatment with dimebon increased the rate of correct choices and decreased the latency of accessing a water reward after water deprivation. Repeated administration of dimebon also increased the duration of drinking behaviour during training/testing procedures although water consumption behaviour was not altered. Additional behavioural tests were carried out to investigate possible non-specific effects of dimebon on parameters of drinking, anxiety and exploration/locomotion. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice. [less ▲]

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice.

in Progress in Neuro-Psychopharmacology & Biological Psychiatry (2011), 35(2), 510-22

Pre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior ... [more ▼]

Pre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior to training in both appetitive and inhibitory learning tasks via repeated (0.1 mg/kg) and acute (0.5 mg/kg) i.p. injections, respectively, increases memory scores. Acute treatment with dimebon was found to enhance inhibitory learning, as also shown in the step-down avoidance paradigm in 7-month-old mice. Bolus administration of dimebon did not affect the animals' locomotion, exploration or anxiety-like behaviour, with the exception of exploratory behaviour in older mice in the novel cage test. In a model of appetitive learning, a spatial version of the Y-maze, dimebon increased the rate of correct choices and decreased the latency of accessing a water reward after water deprivation, and increased the duration of drinking behaviour during training/testing procedures. Repeated treatment with dimebon did not alter the behaviours in other tests or water consumption. Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice. [less ▲]