Preference For Sweet Solutions Research Articles

Supplementation effects of a kokumi substance, γ-Glu-Val-Gly, on the ingestion of basic taste solutions in rats

In addition to the well-accepted taste receptors corresponding to the 6 basic taste qualities, sweet, salty, sour, bitter, umami, and fatty, another type of taste receptor, calcium-sensing receptor (CaSR), is located in taste bud cells. CaSR is called the kokumi receptor because its agonists induce koku (or kokumi), a Japanese word meaning the enhancement of flavor characteristics, such as thickness, mouthfulness, and continuity. Kokumi is an important factor in enhancing food palatability. γ-Glu-Val-Gly (EVG) is the most potent agonist of CaSR, which induces a strong kokumi flavor. However, no behavioral studies have been documented in animals using EVG. Here, we show that EVG at low concentrations that do not elicit a taste of its own enhances preferences for umami, fat, and sweet taste solutions in rats. An increased preference for inosine monophosphate (IMP) and Intralipos was the most dominant effect. NPS-2143, an antagonist of CaSR, abolished the additive effect of EVG on IMP and Intralipos solutions. These effects of EVG on taste stimuli are thought to occur in the oral cavity, because the effects of EVG were confirmed in a brief exposure test. The additive effects on IMP and Intralipos remained after the transection of the chorda tympani, indicating that these effects also occur in the palate and/or posterior part of the tongue. Moreover, the additive effects of EVG were verified in electrophysiological taste nerve responses. These results may partially provide the underlying mechanisms for EVG to induce kokumi flavor in humans.

Behavioral and accumbens synaptic plasticity induced by cues associated with restraint stress.

Exposure to acute stress can increase vulnerability to develop or express many psychiatric disorders, including post-traumatic stress disorder. We hypothesized that stress-induced psychiatric vulnerability is associated with enduring neuroplasticity in the nucleus accumbens core because stress exposure can alter drug addiction-related behaviors that are associated with accumbens synaptic plasticity. We used a single 2-h stress session and 3 weeks later exposed male and female rats to stress-conditioned odors in a modified defensive burying task, and quantified both active and avoidant coping strategies. We measured corticosterone, dendritic spine and astrocyte morphology in accumbens, and examined reward sensitivity using a sucrose two-bottle choice and operant sucrose self-administration. Exposure to stress odor increased burying (active coping) and immobility (avoidant coping) in the defensive burying task in female and male rats. Systemic corticosterone was transiently increased by both ongoing acute restraint stress and stress-conditioned odors. Three weeks after administering acute restraint stress, we observed increased dendritic spine density and head diameter, and decreased synaptic association with astroglia and the astroglial glutamate transporter, GLT-1. Exposure to conditioned stress further increased head diameter without affecting spine density or astroglial morphology, and this increase by conditioned stress was correlated with burying behavior. Finally, we found that stress-exposed females have a preference for sweet solutions and higher motivation to seek sucrose than stressed male rats. We conclude that acute stress produced enduring plasticity in accumbens postsynapses and associated astroglia. Moreover, conditioned stress odors induced active behavioral coping strategies that were correlated with dendritic spine morphology.

Live predator stress in adolescence results in distinct adult behavioral consequences and dorsal diencephalic brain activation patterns

Exposure to traumatic events during childhood increases the risk of adult psychopathology, including anxiety, depression, alcohol use disorders and their co-morbidity. Early life trauma also results in increased symptom complexity, treatment resistance and poor treatment outcomes. The purpose of this study was to establish a novel rodent model of adolescent stress, based on an ethologically relevant life-threatening event, live predator exposure. Rats were exposed to a live predator for 10 min. at three different time points (postnatal day (PND)31, 46 and 61). Adult depression-, anxiety-like behaviors and ethanol consumption were characterized well past the last acute stress event (two weeks). Behavioral profiles across assessments were developed to characterize individual response to adolescent stress. CNS activation patterns in separate groups of subjects were characterized after the early (PND31) and last predator exposure (PND61). Subjects exposed to live-predator adolescent stress generally exhibited less exploratory behavior, less propensity to venture into open spaces, a decreased preference for sweet solutions and decreased ethanol consumption in a two-bottle preference test. Additional studies demonstrated blunted cortisol response and CNS activation patterns suggestive of habenula, rostromedial tegmental (RMTg), dorsal raphe and central amygdala involvement in mediating the adult consequences of adolescent stress. Thus, adolescent stress in the form of live-predator exposure results in significant adult behavioral and neurobiological disturbances. Childhood trauma, its impact on neurodevelopment and the subsequent development of mood disorders is a pervasive theme in mental illness. Improving animal models and our neurobiological understanding of the symptom domains impacted by trauma could significantly improve treatment strategies.

Differential Effects of Maternal High Fat Diet During Pregnancy and Lactation on Taste Preferences in Rats.

Maternal intake of high fat diet (HFD) increases risk for obesity and metabolic disorders in offspring. Developmental programming of taste preference is a potential mechanism by which this occurs. Whether maternal HFD during pregnancy, lactation, or both, imposes greater risks for altered taste preferences in adult offspring remains a question, and in turn, was investigated in the present study. Four groups of offspring were generated based on maternal HFD access: (1) HFD during pregnancy and lactation (HFD); (2) HFD during pregnancy (HFD-pregnancy); (3) HFD during lactation (HFD-lactation); and (4) normal diet (ND) during pregnancy and lactation (ND). Adult offspring 70 days of age underwent sensory and motivational taste preference testing with various concentrations of sucrose and Intralipid solutions using brief-access automated gustometers (Davis-rigs) and 24 h two-bottle choice tests, respectively. To control for post-gestational diet effects, offspring in all experimental groups were weaned on ND, and did not differ in body weight or glucose tolerance at the time of testing. Offspring exposed to maternal HFD showed increased sensory taste responses for 0.3, 0.6, 1.2 M sucrose solutions in HFD and 0.6 M in HFD-pregnancy groups, compared to animals exposed to ND. Similar effects were noted for lower concentrations of Intralipid in HFD (0.05, 0.10%) and HFD-pregnancy (0.05, 0.10, 0.5%) groups. The HFD-lactation group showed an opposite, diminished responsiveness for sucrose at the highest concentrations (0.9, 1.2, 1.5 M), but not for Intralipid, compared to ND animals. Extended-access two-bottle tests did not reveal major difference across the groups. Our study shows that maternal HFD during pregnancy and lactation has markedly different effects on preferences for palatable sweet and fatty solutions in adult offspring and suggests that such developmental programing may primarily affect gustatory mechanisms. Future studies are warranted for determining the impact of taste changes on development of obesity and metabolic disorders in a “real” food environment with food choices available, as well as to identify specific underlying mechanisms.

Proposing the sweet solution preference test as a screening assay for anti-manic effects of mood stabilizers

BackgroundThere is a desperate need for in-vivo behavioral screening tests for anti-manic effects. The frequently used psychostimulant-induced hyperactivity test appears to have lower validity than previously described, but other quick, simple and high throughput tests are currently unavailable. New methodIn the context of modeling the behavioral facets of mania, we previously suggested that the sweet solution preference test (SSP) in naive mice might have predictive validity for screening anti-manic effects. The current study further examined this proposal by testing the effects of lithium, valproate and imipramine on SSP in three strains of mice (male mice from the black Swiss, ICR and C57bl/6 strains) and an exploratory test in females (black Swiss strain). ResultsData demonstrate that lithium and valproate at appropriate dosing schedules significantly and reliably reduce SSP in all three strains (including in females) but that the antidepressant imipramine has no effects. Comparison with existing methodsThe results support the utilization of the SSP as mice screening model for anti-manic effects of drugs with stronger predictive validity compared with other methods. ConclusionsThe SSP is not a comprehensive model for bipolar disorder but it has good predictive validity and strong practical value that can be applied towards simple and fast screening of large numbers of animals, without the need for specialized equipment or complicated/prolonged procedures. We therefore propose that the SSP is an advantageous screening assay for testing novel mood stabilizing drugs for anti-manic properties.

Kamikihito Enhances Cognitive Functions and Reward-Related Behaviors of Aged C57BL/6J Mice in an Automated Behavioral Assay System.

The cognitive and psychological domains of frailty in the elderly have drawn increasing attention given the aging of society. However, therapeutics to treat minor deficits in cognition and mental state in the elderly remain an unmet need. Kamikihito (KKT), a traditional Japanese Kampo medicine indicated for neuroses, anxiety, and insomnia, is effective for treating cognitive dysfunction and depressive-like behaviors in animal models, suggesting that it may have therapeutic potential for treating cognitive and/or mental frailty. In this study, we first validated the known anxiolytic effects of KKT in a conventional maze test. We then introduced an automated behavioral assay system, IntelliCage, to evaluate the therapeutic potential of KKT for age-related and diverse central functions by performing sequential behavioral tasks in young and aged mice to assess basal activities, cognitive functions, perseveration, and hedonic-related behaviors. Although young mice treated with KKT did not exhibit changes in diurnal variation, KKT-administered aged mice exhibited an accelerated decline in voluntary activity during the early part of the light period, implying that KKT may promote sleep onset in aged mice. Neither place learning acquisition for gaining rewards nor subsequent behavioral flexibility performance was altered by KKT in the young group, whereas the aged KKT group exhibited significantly enhanced performance in both phases of learning relative to age-matched controls. Conversely, perseverative nose-pokes (NPs) to gain rewards observed during place learning, indicative of compulsivity, were attenuated by KKT in both age groups. Regarding hedonic processing, aged mice exhibited a decreased preference for sweet solutions compared to young mice, which was effectively reversed by KKT treatment. Furthermore, KKT elevated high-effort choices for high-value reward in an effort-based decision-making paradigm in both age groups, implying augmentation of motivational behaviors by KKT. Collectively, KKT exerted various beneficial effects in cognitive and emotional domains, several of which were more evident in aged mice than in young mice, suggesting the potential of KKT for treating cognitive and mental frailty.

Recovery of stress-impaired social behavior by an antagonist of the CRF binding protein, CRF6−33, in the bed nucleus of the stria terminalis of male rats

Social stress is recognized to promote the development of neuropsychiatric and mood disorders. Corticotropin releasing factor (CRF) is an important neuropeptide activated by social stress, and it contributes to neural and behavioral adaptations, as indicated by impaired social interactions and anhedonic effects. Few studies have focused on the role of the CRF binding protein (CRFBP), a component of the CRF system, and its activity in the bed nucleus of stria terminalis (BNST), a limbic structure connecting amygdala and hypothalamus. In this study, animals’ preference for sweet solutions was examined as an index of stress-induced anhedonic responses in Wistar rats subjected to four brief intermittent episodes of social defeat. Next, social approach was assessed after local infusions of the CRFBP antagonist, CRF fragment 6–33 (CRF6–33) into the BNST. The experience of brief episodes of social defeat impaired social approach behaviors in male rats. However, intra-BNST CRF6–33 infusions restored social approach in stressed animals to the levels of non-stressed rats. CRF6–33 acted selectively on social interaction and did not alter general exploration in nether stressed nor non-stressed rats. These findings suggest that BNST CRFBP is involved in the modulation of anxiety-like responses induced by social stress.

Preliminary Evidence of Apathetic-Like Behavior in Aged Vesicular Monoamine Transporter 2 Deficient Mice.

Apathy is considered to be a core feature of Parkinson’s disease (PD) and has been associated with a variety of states and symptoms of the disease, such as increased severity of motor symptoms, impaired cognition, executive dysfunction and dementia. Apart from the high prevalence of apathy in PD, which is estimated to be about 40%, the underlying pathophysiology remains poorly understood and current treatment approaches are unspecific and proved to be only partially effective. In animal models, apathy has been sub-optimally modeled, mostly by means of pharmacological and stress-induced methods, whereby concomitant depressive-like symptoms could not be ruled out. In the context of PD only a few studies on toxin-based models (i.e., 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)) claimed to have determined apathetic symptoms in animals. The assessment of apathetic symptoms in more elaborated and multifaceted genetic animal models of PD could help to understand the pathophysiological development of apathy in PD and eventually advance specific treatments for afflicted patients. Here we report the presence of behavioral signs of apathy in 12 months old mice that express only ~5% of the vesicular monoamine transporter 2 (VMAT2). Apathetic-like behavior in VMAT2 deficient (LO) mice was evidenced by impaired burrowing and nest building skills, and a reduced preference for sweet solution in the saccharin preference test, while the performance in the forced swimming test was normal. Our preliminary results suggest that VMAT2 deficient mice show an apathetic-like phenotype that might be independent of depressive-like symptoms. Therefore VMAT2 LO mice could be a useful tool to study the pathophysiological substrates of apathy and to test novel treatment strategies for apathy in the context of PD.

Differential effects of photoperiod length on depression- and anxiety-like behavior in female and male diurnal spiny mice

The relationships between biological rhythms and affective disorders are known but their underlying biology not clear. There is difficulty in studying circadian rhythms in humans and appropriate animal models are hard to identify or develop. Some studies show that diurnal rodents can be advantageous model animals for the study of interactions between biological rhythms and affective disorders but previous studies did not include females whereas in humans there are sex differences in affective disorders. The present study tested the effects of short photoperiods in both males and females of the diurnal golden spiny mouse (Acomys russatus).Adult, female and male spiny mice were housed in either neutral photoperiod (12:12 light/dark; NP), or short photoperiod (5:19 light/dark; SP) conditions. After 3weeks acclimatization, animals were tested for spontaneous activity in an open field, elevated plus maze (EPM), sweet solution preference (SSP) and the forced swim test (FST).Both sexes responded to the SP, but while SP males showed increased anxiety-like behavior in the EPM and depression-like behavior in the FST, females showed increased activity, reduced anxiety-like behavior in the EPM, depression-like response in the SSP and no effect in the FST.Differences between sexes were previously demonstrated in behavioral tests that followed a variety of manipulations, and were usually explained in the context of sex hormones. Yet, the current results cannot be compared with previous data from diurnal rodents and further testing of females from other diurnal rodents are needed to explore whether these differences are a general phenomenon or possibly unique to golden spiny mice.

Homer2 within the nucleus accumbens core bidirectionally regulates alcohol intake by both P and Wistar rats

In murine models of alcoholism, the glutamate receptor scaffolding protein Homer2 bidirectionally regulates alcohol intake. Although chronic alcohol drinking increases Homer2 expression within the core subregion of the nucleus accumbens (NAc) of alcohol-preferring P rats, the relevance of this neuroadaptation for alcohol intake has yet to be determined in rats. Thus, the present study employed an adeno-associated viral vector (AAV) strategy to over-express and knock down the major rodent isoform Homer2b within the NAc of both P and outbred Wistar rats to examine for changes in alcohol preference and intake (0–30% v/v) under continuous-access procedures. The generalization of AAV effects to non-drug, palatable, sweet solutions was also determined in tests of sucrose (0–5% w/v) and saccharin (0–0.125% w/v) intake/preference. No net-flux in vivo microdialysis was conducted for glutamate in the NAc to relate Homer2-dependent changes in alcohol intake to extracellular levels of glutamate. Line differences were noted for sweet solution preference and intake, but these variables were not affected by intra-NAc AAV infusion in either line. In contrast, Homer2b over-expression elevated, while Homer2b knock-down reduced, alcohol intake in both lines, and this effect was greatest at the highest concentration. Strikingly, in P rats there was a direct association between changes in Homer2b expression and NAc extracellular glutamate levels, but this effect was not seen in Wistar rats. These data indicate that NAc Homer2b expression actively regulates alcohol consumption by rats, paralleling this previous observation in mice. Overall, these findings underscore the importance of mesocorticolimbic glutamate activity in alcohol abuse/dependence and suggest that Homer2b and/or its constituents may serve as molecular targets for the treatment of these disorders.

The effects of the atypical antipsychotic asenapine in a strain-specific battery of tests for mania-like behaviors.

Asenapine is indicated for the treatment of schizophrenia and manic episodes in bipolar disorder (BPD). There is a paucity of information on the effects of asenapine in animal models of BPD, but such work is essential to discover its scope of effects and its mechanisms of therapeutic action. This study evaluated the effects of asenapine in a validated test battery for manic-like behaviors in Black Swiss mice. Male Black Swiss mice received asenapine at 0.03, 0.1, and 0.3 mg/kg twice daily for 7 days and were tested for spontaneous activity, sweet solution preference, forced-swim test, social interaction, and amphetamine-induced hyperactivity. Asenapine treatment resulted in dose-dependent, clinically relevant plasma levels. Asenapine, at the 0.1 and 0.3 mg/kg doses, reduced activity, with the 0.3 mg/kg dose also resulting in increased time in the center of an open field, increased immobility in the forced-swim test, and reduced amphetamine-induced hyperactivity. Asenapine exerted no effects in the social interaction or sweet solution preference tests. The results suggest that asenapine exerts antimanic-like effects in some of the behavioral tests performed in Black Swiss mice. These data support the utilization of asenapine in the treatment of BPD.

Introducing Female Black Swiss Mice: Minimal Effects of Sex in a Strain-Specific Battery of Tests for Mania-Like Behavior and Response to Lithium

Black Swiss (BS) mice were shown to be an advantageous strain to model behavioral domains of mania, but to date only male mice were tested, whereas bipolar disorder (BPD) is equally prevalent in women and men. This study was therefore designed to examine the possibility of using both male and female BS mice in future studies. Groups of male and female BS mice were compared with each other, with or without lithium treatment, in tests for domains of mania-like behavior including activity in an open field, sweet solution preference, elevated plus maze, forced swim and amphetamine-induced hyperactivity. The results indicate mostly a similarity between female and male BS mice, both naïve and after chronic lithium treatment. The results are discussed in the context of the deficiency in utilizing female mice in animal models research and suggest that both male and female BS mice can be used to model domains of mania-like behavior.

Partial effects of the AMPAkine CX717 in a strain specific battery of tests for manic-like behavior in black Swiss mice.

AMPA receptors are highly expressed throughout the central nervous system and are suggested to be involved in mood regulation. Studies found changes in glutamate, its metabolites and receptors in patients with bipolar disorder (BPD) or major depression (MD) and in animal models of stress. Additional data suggest that the glutamatergic system and AMPA receptors specifically, have an important role in modulating the therapeutic effects of mood stabilizers. Further research on the role of AMPA receptors in mood regulation can be done using AMPAkines, positive modulators of AMPA receptors. AMPAkines have been studied for cognitive enhancement in neurodegenerative disorders and some were also examined in preclinical studies of mood disorders. In that context, the present study was designed to test the effects of the AMPAkine CX717 in a strain specific battery of tests for mania-like behaviors. Black Swiss male mice were sub-chronically treated with 5 different doses of CX717 or vehicle and tested in a battery of behavioral tests including spontaneous activity, sweet solution preference, resident-intruder, forced swim and amphetamine-induced hyperactivity. Data show that CX717 doses of 30mg/kg and above, but not lower, reduce activity levels. Moreover, 45mg/kg and above reduce interactions in the resident-intruder test and ameliorate amphetamine-induced hyperactivity. The results therefore show a partial effect of CX717 on manic-like behavior, somewhat similar to previously demonstrated effects of atypical antipsychotic drugs in this strain. It is therefore suggested that further work related to AMPAkines in the treatment of affective disorders might be warranted.

Effect of a long-term exposure to concentrated sucrose and maltodextrin solutions on the preference, appetence, feed intake and growth performance of post-weaned piglets

Commercial pigs display an innate attraction for sweet taste compounds. However, the impact of long-term availability to supplementary carbohydrate solutions on their general feeding behavior has not been examined. In this work we assess the effect of 12-days exposure to 16% sucrose and 16% maltodextrin solutions on the feed intake and growth performance of piglets, and on their preference and appetence for sweet or protein solutions. The innate preference of piglets was assessed by an initial choice test between 2% sucrose and 2% animal plasma solutions for a period of three minutes. Piglets showed higher intake and preference for 2% sucrose than for 2% animal plasma. In Experiment 1, piglets were then free-offered a 16% sucrose solution as a supplement to the diet, showing a higher intake of it than water and a reduction in feed intake and weight gain. A similar situation occurred during the last days of free-exposure to a 16% maltodextrin solution in Experiment 2. The choice test between 2% sucrose and 2% animal plasma solution was repeated after the exposure to the concentrated solutions. In both experiments, a reduction in the initial preference for 2% sucrose was observed. Similarly, piglets that had previous access to the 16% sucrose and 16% maltodextrin solutions showed a decrease in the appetence for 2% sucrose in comparison with that for 2% animal plasma, as measured by a one-pan test at the end of the experiments. It is concluded that long-term exposure to concentrated sucrose and maltodextrin solutions reduces feed intake and growth in weanling piglets, and also reverses their innate preference and appetence for dilute sweet over protein solutions.

Attenuated orexinergic signaling underlies depression-like responses induced by daytime light deficiency

Light has profound effects on mood, as exemplified by seasonal affective disorder (SAD) and the beneficial effects of bright light therapy. However, the underlying neural pathways through which light regulates mood are not well understood. Our previous work has developed the diurnal grass rat, Arvicanthis niloticus, as an animal model of SAD (Leach et al., 2013a,b). By utilizing a 12:12-h dim light:dark (DLD) paradigm that simulates the lower light intensity of winter, we showed that the animals housed in DLD exhibited increased depression-like behaviors in the forced swim test (FST) and sweet solution preference (SSP) compared to animals housed in bright light during the day (BLD). The objective of the present study was to test the hypothesis that light affects mood by acting on the brain orexinergic system in the diurnal grass rat model of SAD. First, orexin A immunoreactivity (OXA-ir) was examined in DLD and BLD grass rats. Results revealed a reduction in the number of OXA-ir neurons in the hypothalamus and attenuated OXA-ir fiber density in the dorsal raphe nucleus of animals in the DLD compared to those in the BLD group. Then, the animals in BLD were treated systemically with SB-334867, a selective orexin 1 receptor (OX1R) antagonist, which led to a depressive phenotype characterized by increased immobility in the FST and a decrease in SSP compared to vehicle-treated controls. Results suggest that attenuated orexinergic signaling is associated with increased depression-like behaviors in grass rats, and support the hypothesis that the orexinergic system mediates the effects of light on mood.

Partial effects of the protein kinase C inhibitor chelerythrine in a battery of tests for manic-like behavior in black Swiss mice

BackgroundThe inhibition of protein kinase C (PKC) was recently suggested as a novel approach for the development of mood stabilizing drugs. MethodsTo further evaluate this possibility, the aim of the present study was to test the effects of peripheral (intraperitoneal) administration of chelerythrine in a battery of mania-related behavioral tests in black Swiss mice, a strain specific battery that was previously demonstrated to distinguish differential effects of mood stabilizing drugs. ResultsSub-chronic administration of 1.0mg/kg or 2.0mg/kg chelerythrine had marginal effects to reduce spontaneous activity and sweet solution preference in black Swiss mice which naturally show mania-like behaviors. Chelerythrine had no effects on the behavior of these mice in the elevated plus-maze, the forced swim test and the amphetamine-induced hyperactivity test. ConclusionsThe partial effects in the battery are not unique as previous studies showed that lithium, valproate and risperidone, all used in the treatment of bipolar disorder, have distinct profiles in the battery. It is therefore concluded that chelerythrine may have antimanic effects and additional dose and time response studies are warranted to further evaluate its range of activity.

Diurnal rodents as an advantageous model for affective disorders: novel data from diurnal degu (Octodon degus)

Circadian rhythms are strongly associated with affective disorders and recent studies have suggested utilization of diurnal rodents as model animal for circadian rhythms-related domains of these disorders. Previous work with the diurnal fat sand rat and Nile grass rat demonstrated that short photoperiod conditions result in behavioral changes including anxiety- and depression-like behavior. The present study examined the effect of manipulating day length on activity rhythms and behavior of the diurnal degu. Animals were housed for 3weeks under either a short photoperiod (5-h:19-h LD) or a neutral photoperiod (12-h:12-h LD) and then evaluated by sweet solution test and the forced swim test for depression-like behavior, and in the light/dark box and open field for anxiety-like behavior. Results indicate that short photoperiod induced depression-like behavior in the forced swim test and the sweet solution preference test and anxiety-like behavior in the open field compared with animals maintained in a neutral photoperiod. No effects were shown in the light/dark box. Short photoperiod-acclimated degu showed reduced total activity duration and activity was not restricted to the light phase. The present study further supports the utilization of diurnal rodents to model circadian rhythms-related affective change. Beyond the possible diversity in the mechanisms underlying diurnality in different animals, there are now evidences that in three different diurnal species, the fat sand rat, the grass Nile rat and the degu, shortening of photoperiod results in the appearance of anxiety- and depression-like behaviors.

Responses of brain and behavior to changing day-length in the diurnal grass rat (Arvicanthis niloticus)

Seasonal affective disorder (SAD) is a major depressive disorder that recurs in the fall and winter when day-length gets short. It is well accepted that day-length is encoded by the principal circadian clock located in the suprachiasmatic nucleus (SCN), but very little is known about day-length encoding in diurnal mammals. The present study utilized the grass rat, Arvicanthis niloticus, to investigate how the circadian system responds to photoperiodic changes in a diurnal mammal that shows day-length-dependent mood changes. The animals were initially housed in equatorial day-length (12h, EP) followed by either long (16h, LP) or short (8h, SP) photoperiods. The LP animals showed an expansion of the peak phase of the PER1 and PER2 rhythm in the SCN as well as an extended behavioral active phase. In contrast, the SP animals did not show any compression of their active phase nor a change in the peak duration of PER1 or PER2 expression, compared to those in EP. The results suggest that the circadian system in the diurnal grass rats is less responsive when day-length gets short compared to when it gets longer. The depression-like behaviors were assessed using sweet solution preference (SSP) and forced swimming test (FST). Animals in the SP group showed decreased SSP and increased immobility time in FST as compared to the EP group, suggesting a depressive phenotype. The present study serves as the first step toward exploring the role that the circadian system plays in SAD using a diurnal rodent model.

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

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.

Behavioral differences in black Swiss mice from separate colonies

Recent work demonstrated the advantages of using black Swiss (BS) mice to model behavioral domains of mania including reward-seeking, risk-taking, vigor, and sensitivity to psychostimulants. Until recently BS mice were only available from Taconic (TAC) farms, but a colony was recently established by Charles River (CR). The present study compared the behavioral phenotype of mice from the new CR colony to the TAC animals to evaluate if mice from CR also have the advantages as model animals for mania. TAC and CR mice were compared in a battery of tests related to domains of mania, and the effects of lithium were tested in the CR mice. CR mice showed lower activity levels and preference for sweet solution and higher immobility in the forced swim test compared with TAC mice. Furthermore, in contrast with the antimanic-like effects of lithium previously described in TAC mice, in CR mice lithium only had an antidepressant-like effect in the forced swim test. The results indicate that the CR BS mice lack the behavioral properties that make the TAC BS mice advantageous for modeling domains of mania.