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.

a b s t r a c t a r t i c l e i n f oPre-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.

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The revived interest of many countries and the growing number of ongoing and scheduled missions to the Moon increases the significance of supporting navigation system development. A number of publications are based on multi-Global Navigation Satellite System (GNSS) signal reception from the opposite side of the Earth using high-gain antennas and lunar augmentation constellations. While the accuracy of such systems could be sufficient, the positioning, navigation, and timing (PNT) service dependency on circumterestrial navigation sources prevents the use of advanced navigation technologies honed in circumlunar space for further Mars and other celestial body missions, which is one of the major goals of lunar exploration. Moreover, orbit determination and time synchronization (ODTS) method descriptions and estimations are usually skipped in the studies of lunar augmentations. An alternative concept of the Lunar Navigation Satellite System (LNSS) is proposed based on Earth-dependency reduction principal and on-board ODTS. The advantage of the proposed approach is that LNSS-like systems could be adapted for other celestial bodies taking into account aspects such as their shape, dynamics, perturbations, as well as exploration priority regions. The baseline LNSS constellation of three circular orbits with three satellites each has been chosen as the result of multicriterion analysis of orbital stability and geometry. Station keeping requires less than 15 m/s for 10 years without significant changes in navigation performance in the prioritized Polar Regions. The full cycle of LNSS operation from ODTS and signal generation to its reception, processing, and obtaining navigation solutions has been simulated to obtain positioning accuracy for different types of users. Positioning accuracy of space users in approach/departure phases, in near-lunar orbits, as well as static users on a lunar surface is confirmed on a level of a few tens of meters. The same accuracy is achievable by dynamic users on a lunar surface during route stops or also in motion in case of LNSS constellation expansion or deployment of ground-based augmentation beacons in on-site exploration zones.