Short day lengths alter stress and depressive-like responses, and hippocampal morphology in Siberian hamsters

Many psychological disorders comprise a seasonal component. For instance, seasonal affective disorder (SAD) is characterized by depression during autumn and winter. Because hippocampal atrophy may underlie the symptoms of depression and depressive-like behaviors, one goal of this study was to determine whether short days also induce structural changes in the hippocampus using photoperiod responsive rodents — Siberian hamsters. Exposure to short days increases depressive-like responses (increased immobility in the forced swim test) in hamsters. Male hamsters were housed in either short (LD 8:16) or long days (LD 16:8) for 10 weeks and tested in the forced swim test. Brains were removed and processed for Golgi impregnation. HPA axis function may account for photoperiod-related changes in depressive-like responses. Thus, stress reactivity was assessed in another cohort of photoperiod-manipulated animals. Short days reduced soma size and dendritic complexity in the CA1 region. Photoperiod did not induce gross changes in stress reactivity, but an acute stressor disrupted the typical nocturnal peak in cortisol concentrations. These data reveal that immobility induced by exposure to short days is correlated with reduced CA1 cell complexity (and perhaps connectivity). This study is the first to investigate hippocampal changes in the context of short-day induced immobility and may be relevant for understanding psychological disorders with a seasonal component.     

High post-partum levels of corticosterone given to dams influence postnatal hippocampal cell proliferation and behavior of offspring: A model of post-partum stress and possible depression

Post-partum stress and depression (PPD) have a significant effect on child development and behavior. Depression is associated with hypercortisolism in humans, and the fluctuating levels of hormones, including corticosterone, during pregnancy and the post-partum, may contribute to PPD. The present study was developed to investigate the effects of high-level corticosterone (CORT) post-partum in the mother on postnatal neurogenesis and behavior in the offspring. Sprague-Dawley dams were treated with either CORT (40 mg/kg) or sesame oil injections daily for 26 days beginning the day after giving birth. Dams were tested in the forced swim test (FST) and in the open field test (OFT) on days 24-26 post-partum. Results showed that the dams exposed to CORT expressed "depressive-like" behavior compared to controls, with decreased struggling behavior and increased immobility in the FST. To investigate the effects of treatment on hippocampal postnatal cell proliferation and survival in the offspring, males and females from treated dams were injected with BrdU (50 mg/kg) on postnatal day 21 and perfused either 24 h (cell proliferation) or 21 days (cell survival) later. Furthermore, male and female offspring from each litter were tested in adulthood on various behavioral tests, including the forced swim test, open field test, resistance to capture test and elevated plus maze. Intriguingly, male, but not female, offspring of CORT-treated dams exhibited decreased postnatal cell proliferation in the dentate gyrus. Both male and female offspring of CORT-treated dams showed higher resistance to capture and greater locomotor activity as assessed in the open field test. As high levels of CORT may be a characteristic of stress and/or depression, these findings support a model of 'CORT-induced' post-partum stress and possibly depression and demonstrate that the offspring of affected dams can exhibit changes in postnatal neurogenesis and behavior in adulthood.     

Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats

The purpose of these experiments was to test the hypothesis that attenuating the endogenous increase of the 5alpha-reduced progesterone metabolite 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) in the hippocampus will alter anxiety and depression behavior of proestrous rats. In Experiment 1, anxiety (open field) and depression (forced swim test) behavior was compared of rats that should have high (proestrous) and low (diestrous and male rats) endogenous hippocampal 3alpha,5alpha-THP. Proestrous rats exhibited more anxiolytic-like (increased central entries in the open field) and anti-depressant-like (less immobility in the forced swim test) behavior than diestrous or male rats. In Experiments 2 and 3, respectively, systemic and intrahippocampal finasteride, a 5alpha-reductase inhibitor which attenuates progesterone's metabolism to 3alpha,5alpha-THP, versus vehicle administration to proestrous rats was compared for effects on open field and forced swim test behavior. Systemic or intrahippocampal finasteride decreased central entries in the open field and increased immobility in the forced swim tests compared to vehicle administration. In Experiment 4, the effects of systemic and intrahippocampal finasteride vs vehicle administration on hippocampal 3alpha,5alpha-THP of proestrous rats was examined. Finasteride, SC or intrahippocampally, reduced 3alpha,5alpha-THP in the hippocampus compared to vehicle administration. Together these data suggest that variations in 3alpha,5alpha-THP levels in the hippocampus may mitigate proestrous changes in anxiety and depressive behavior of cycling rats.     

Repeated electroconvulsive stimuli have long-lasting effects on hippocampal BDNF and decrease immobility time in the rat forced swim test

Electroconvulsive therapy is considered an effective treatment for severe depression. However, the mechanisms for its long-lasting antidepressant efficacy are poorly understood. In the present study, we investigated changes of the immobility time in the forced swim test and brain-derived neurotrophic factor (BDNF) protein after withdrawal from 14-day repeated electroconvulsive stimuli (ECS, 50 mA, 0.2 s) in rats. Immobility time in the forced swim test was markedly decreased 6 h after withdrawal following 14-day ECS treatment. Thereafter, prolongation of the withdrawal period gradually diminished the decreasing effect of immobility time, but significant effects persisted for up to 3 days after the withdrawal. Locomotor activity in the open-field test increased 6 h after withdrawal from the ECS treatment, and the enhanced effect persisted for at least 7 days. The BDNF protein level in the hippocampus was markedly increased 6 h after the withdrawal, and remained high for at least 7 days. These findings provide further evidence that repeated ECS has long-lasting effect on increase in BDNF and locomotor activity and decrease in immobility time in the forced swim test.     

Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and cAMP signaling in hippocampus

[Purpose]

Mood disorders such as anxiety and depression are prevalent psychiatric illness, but the role of 5HT1A in the anti-depressive effects of exercise has been rarely known yet. We investigated whether long-term exercise affected a depressive-like behavior and a hippocampal 5HT1A receptor-mediated cAMP/PKA/CREB signaling in depression mice model.

[Methods]

To induce depressive behaviors, mice were subjected to 14 consecutive days of restraint stress (2 hours/day). Depression-like behaviors were measured by forced swimming test (TST), and anxiety-like behavior was assessed by elevated plus maze (EPM). Treadmill exercise was performed with 19 m/min for 60 min/day, 5 days/week from weeks 0 to 8. Restraint stress was started at week 6 week and ended at week 8. To elucidate the role of 5HT1A in depression, the immunoreactivities of 5HT1A were detected in hippocampus using immunohistochemical technique.

[Results]

Chronic/repeated restraint stress induced behavioral anxiety and depression, such as reduced time and entries in open arms in EPM and enhanced immobility time in FST. These anxiety and depressive behaviors were ameliorated by chronic exercise. Also, these behavioral changes were concurrent with the deficit of 5HT1A and cAMP/PKA/CREB cascade in hippocampus, which was coped with chronic exercise.

[Conclusion]

These results suggest that chronic exercise may improve the disturbance of hippocampal 5HT1A-regulated cAMP/PKA/CREB signaling in a depressed brain, thereby exerting an antidepressive action.     

Short-day photoperiod disrupts daily activity and facilitates anxiety–depressive behaviours in gerbil Meriones unguiculatus

Seasonal photoperiod has impact on the physiology of many plants and animals. Short days related with the winter are often associated with changes in activity patterns and, in humans, with some mood disorders. Natural changes related with seasonality occur gradually and such approach has to be considered when studying animal models in laboratory conditions. In the present work, we studied if gradual changes from light–dark cycles 12:12 h to short (08:16) or long days (16:08) have a significant effect upon the locomotor activity profile and some anxiety- and depression-like behaviours in the gerbil Meriones unguiculatus. Locomotor activity was recorded by means of infrared light beams. Once adapted to experimental photoperiod, gerbils were used for elevated plus maze (EPM) or forced swim test (FST). Our results indicate that in 12:12, a clear bimodal pattern associated with light transitions was present. When exposed to long days, gerbils increased their total locomotor activity and the bimodal profile persisted. When in short days, locomotor activity decreased and no rhythm was noted. Behavioural assays on EPM and FST indicated that exposition to short days induce in the gerbils an anxiety and depressive-like behaviour, reducing the time spent in open arms and increasing the time of immobilizations. We conclude that short photoperiod affects negatively the locomotor activity daily patterns and mood behaviour in anxiety and depressive way in the Mongolian gerbil.     

Effect of a Selective Cyclooxygenase Type 2 Inhibitor Celecoxib on Depression Associated with Obesity in Mice: An Approach Using Behavioral Tests

The biological mechanisms that link the development of depression to metabolic disorders such as obesity and diabetes remain ambiguous. In the present study the potential of a selective cyclooxygenase inhibitor celecoxib (15 mg/kg p.o.) was investigated in depression associated with obesity in mice. Behavioral tests used to assess depressive-like behavior were sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM). The basal locomotor score in obese mice was not altered. Furthermore, estimation of biochemical parameters was performed for plasma glucose, total cholesterol, triglycerides and total proteins. Escitalopram (10 mg/kg p.o.) served as reference standard drug. In the results, chronic treatment with celecoxib for 28 days significantly attenuated the behavioral alterations as indicated by increased the sucrose consumption, reduced the immobility time in FST and TST, increased the percent open arm time and entries in EPM in obese mice. In the biochemical parameters celecoxib significantly reversed the increased plasma glucose, total cholesterol, triglycerides and total proteins in obese mice. In conclusion, celecoxib exhibited potential antidepressant-like effect in depression associated with obesity, which to some extent is mediated by reversing the altered plasma glucose in obese mice.     

Antidepressants stimulate hippocampal neurogenesis by inhibiting p21 expression in the subgranular zone of the hipppocampus

The relationships among hippocampal neurogenesis, depression and the mechanism of action of antidepressant drugs have generated a considerable amount of controversy. The cyclin-dependent kinase (Cdk) inhibitor p21(Cip1) (p21) plays a crucial role in restraining cellular proliferation and maintaining cellular quiescence. Using in vivo and in vitro approaches the present study shows that p21 is expressed in the subgranular zone of the dentate gyrus of the hippocampus in early neuronal progenitors and in immature neurons, but not in mature neurons or astroglia. In vitro, proliferation is higher in neuronal progenitor cells derived from p21-/- mice compared to cells derived from wild-type mice. Proliferation is increased in neuronal progenitor cells after suppression of p21 using lentivirus expressing short hairpin RNA against p21. In vivo, chronic treatment with the non-selective antidepressant imipramine as well as the norepinephrine-selective reuptake inhibitor desipramine or the serotonin-selective reuptake inhibitor fluoxetine all decrease p21 expression, and this was associated with increased neurogenesis. Chronic antidepressant treatment did not affect the expression of other Cdk inhibitors. Untreated p21-/- mice exhibit a higher degree of baseline neurogenesis and decreased immobility in the forced swim test. Although chronic imipramine treatment increased neurogenesis and reduced immobility in the forced swim test in wild-type mice, it reduced neurogenesis and increased immobility in p21-/- mice. These results demonstrate the unique role of p21 in the control of neurogenesis, and support the hypothesis that different classes of reuptake inhibitor-type antidepressant drugs all stimulate hippocampal neurogenesis by inhibiting p21 expression.     

Increased depressive-like traits in an animal model of premenstrual irritability

Women are at higher risk of anxiety and mood disorders, especially at transitions across the reproductive life cycle (premenstruum, postpartum, menopause). Premenstrual dysphoric disorder (PMDD) is one of female mood disorders associated with changing ovarian hormone levels. Because anxiety and depression frequently occur in women with PMDD, premenstrual dysphoria might be a manifestation of certain vulnerability traits increasing the risk of those disorders. The present study was conducted to elucidate a potential association between estrous cycle-dependent aggression, the rodent model of "premenstrual irritability" (resident-intruder test), and anxiety (elevated plus maze), depressive-like traits (forced swim test) as well as carbohydrate craving in female Wistar rats. Some aggressive and nonaggressive females were restraint-stressed before testing to determine their sensitivity to stress at different hormonal stages. The results revealed that females expressing the estrous cycle-dependent aggression but not those not expressing cycle-dependent aggression spent longer time immobile and shorter time swimming in the forced swim test at metestrus compared to proestrus phase of the estrous cycle. There was no difference between aggressive and nonaggressive females in anxiety, locomotor activity and sensitivity to restraint stress and sucrose consumption. The present study suggests a common neurobiological background for the estrous cycle-dependent aggression and depressive-like traits in rodents. This phenomenon could potentially aid the elucidation of premenstrual emotional dysfunctions and might be used as an ethological model to study a biochemical and genetic proneness to depression.     

Impact of High-Fat Diet and Early Stress on Depressive-Like Behavior and Hippocampal Plasticity in Adult Male Rats

During development, the brain goes through fundamental processes, including organization of neural networks and plasticity. Environmental interventions may change initial brain programming, leading to long-lasting effects and altering the susceptibility to psychopathologies, including depression disorder. It is known that depression is a psychiatric disorder with a high prevalence worldwide, including high rates among adolescents. In this study, we evaluated whether social isolation in the prepubertal period and chronic use of high-fat diet (HFD) may induce depressive-like behavior in male adult rats. We also investigated hippocampal plasticity markers and neurotransmitter systems. We found both social isolation and HFD induced a depressive-like behavior in the forced swimming task. Moreover, chronic HFD reduced synaptic markers in hippocampus, demonstrated by reductions in βIII-tubulin (neuronal marker), PSD-95, SNAP-25, and neurotrophin-3. The HFD group also presented decreased glutamatergic and GABAergic receptors subunits. On the other hand, stress affected hippocampal brain-derived neurotrophic factor (BDNF) signaling pathways, and increased expression of subunit of the NMDA receptor (NR2A). Both factors (stress and diet) decreased GR in the hippocampus without affecting plasma corticosterone at basal levels. Interactions between early stress and HFD access were observed only in the BNDF receptor (tropomyosin receptor kinase B; TrkB) and synaptophysin. In summary, these findings showed that a brief social isolation and chronic HFD, during a sensitive developmental period, cause depressive-like behavior in adulthood. The mechanisms underlying these behavioral effects may involve changes in the levels of synaptic proteins in hippocampus: HFD consumption appears to affect synaptic markers, while social isolation affected BDNF signaling more significantly.     

Photoperiodic and hormonal influences on fur density and regrowth in two hamster species

Temperate and boreal mammals undergo seasonal changes in pelage that facilitate thermoregulation in winter and summer. We investigated photoperiodic influences on pelage characteristics of male Siberian and Syrian hamsters. Fur density (mg fur/cm2 skin) was measured by weighing the shavings of fur patches removed from the dorsal and ventral surfaces of hamsters maintained in long days (LDs) or transferred to short days (SDs). Patches were reshaved 3 wk later to assess fur regrowth (mg regrown fur/cm2 skin). Fur density was greater in SD than in LD Siberian hamsters after 11 wk of differential phototreatment. The onset of increased fur density in SDs was accompanied by a transient increase in fur regrowth (11-14 wk on the dorsal surface and 7-10 and 11-14 wk on the ventral surface), suggestive of a seasonal molting process. Fur density, body mass, and pelage color of Siberian hamsters returned to values characteristic of LD males after a similar duration of prolonged (>27 wk) SD treatment and appear to be regulated by a similar or common interval-timing mechanism. In Syrian hamsters, dorsal fur density, fur regrowth, and hair lengths were greater in SD than in LD males. Castration increased and testosterone (T) treatment decreased dorsal and ventral fur regrowth in LD and SD hamsters, but the effects of T manipulations on fur density were limited to a decrease in dorsal fur density after T treatment. Decreased circulating T in SDs likely contributes to the seasonal molt of male hamsters by increasing the rate of fur growth during the transition to the winter pelage.     

Effects of rTMS on Hippocampal Endocannabinoids and Depressive-like Behaviors in Adolescent Rats

Depression is a common mental disorder in adolescents, with a prevalence rate of 5.6%. Current anti-depressive options for adolescents are limited: psychological intervention and conventional antidepressants have low efficacy, a delayed onset of action and increased possibility of suicidal risk. Repetitive transcranial magnetic stimulation (rTMS) as an effective and noninvasive physical therapy for adult depression has been investigated in recent years. However, whether it also produces similar effects on juvenile depression and the underlying mechanism are not clearly understood. In this study, chronic unpredictable mild stress (CMS) was applied to 3-week-old male Sprague Dawley rats for 21 days. Then rTMS was performed for seven consecutive days, and the anti-depressive effects were evaluated by behavioral tests including the sucrose preference test (SPT), the forced swimming test (FST), and the novelty suppressed feeding test (NSF). Expression of hippocampal cannabinoid type I receptor (CB1R), 2-arachidonoylglycerol (2-AG) and relative synthetase and degradative enzymes-diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL) were also investigated. The behavioral parameters were also observed after the administration of the selective CB1 receptor antagonist AM251. The results showed that CMS induced a significant decrease in sucrose preference, a significant increase of immobility time in the FST, and an increased latency to feed in the NSF. In addition, reduced hippocampal CB1 receptor, 2-AG level and increased MAGL protein expression level were also observed in CMS rats. Meanwhile, rTMS treatment upregulated 2-AG level in the hippocampus and ameliorated depressive-like behaviors. The anti-depressive effect of rTMS was attenuated by AM251, a specific CB1R antagonist that was administered 30 min before the onset of rTMS by either intraperitoneal administration or hippocampal microinjection. These results indicate that rTMS can be used as an antidepressive therapy for juvenile depression at least partly mediated by increasing hippocampal 2-AG and CB1 receptor expression levels.     

Behavioral effects of chronic adolescent stress are sustained and sexually dimorphic

Evidence suggests that women are more susceptible to stress-related disorders than men. Animal studies demonstrate a similar female sensitivity to stress and have been used to examine the underlying neurobiology of sex-specific effects of stress. Although our understanding of the sex-specific effects of chronic adolescent stress has grown in recent years, few studies have reported the effects of adolescent stress on depressive-like behavior. The purpose of this study was to determine if a chronic mixed modality stressor (consisting of isolation, restraint, and social defeat) during adolescence (PND 37-49) resulted in differential and sustained changes in depressive-like behavior in male and female Wistar rats. Female rats exposed to chronic adolescent stress displayed decreased sucrose consumption, hyperactivity in the elevated plus maze, decreased activity in the forced swim test, and a blunted corticosterone response to an acute forced swim stress compared to controls during both adolescence (PND 48-57) and adulthood (PND 96-104). Male rats exposed to chronic adolescent stress did not manifest significant behavioral changes at either the end of adolescence or in adulthood. These data support the proposition that adolescence may be a stress sensitive period for females and exposure to stress during adolescence results in behavioral effects that persist in females. Studies investigating the sex-specific effects of chronic adolescent stress may lead to a better understanding of the sexually dimorphic incidence of depressive and anxiety disorders in humans and ultimately improve prevention and treatment strategies.     

Amphetamine withdrawal: a behavioral evaluation

The effects of withdrawal from long-term amphetamine treatment of intracranial self-stimulation, forced swim-induced immobility, shuttle escape performance, acoustic startle and locomotor activity were evaluated. Mice implanted with stimulating electrodes in the lateral hypothalamus demonstrated stable and reliable rates of self-stimulation responding. After exposure to a chronic schedule of amphetamine treatment response rates were severely depressed. In addition to modifying intracranial self-stimulation responding, amphetamine withdrawal increased the duration of immobility in a forced-swim situation. Although chronic amphetamine exposure induced pronounced behavioral changes in the intracranial self-stimulation and forced swim tasks, drug withdrawal had little effect on shuttle escape performance, acoustic startle and locomotor activity. Based on these findings it was suggested that the development of post-amphetamine depression in the self-stimulation and forced swim paradigms was not related to variations in motoric or arousal mechanisms resulting from amphetamine withdrawal, but rather involved drug-induced changes in motivational processes.     

Circadian and Seasonal Variations of Plasma Insulin and Cortisol Concentrations in the Syrian Hamster, Mesocricetus Auratus

Circadian rhythms of plasma insulin, Cortisol, and glucose concentrations were examined in scotosensitive (reproductively sensitive to inhibitory effects of short daylengths) and scotorefractory male and female Syrian hamsters (Mesocricetus auratus) maintained on short (LD 10:14) and long (LD 14:10) daylengths. The baseline concentration (mean of all values obtained every 4 hr six times of day) of insulin was much greater in female than in male scotosensitive hamsters kept on short daylengths. These differences in insulin concentration may account for the observed heavy fat stores in female and low fat stores in male scotosensitive hamsters kept on short daylengths. The baseline concentrations of Cortisol were approximately equal in both scotosensitive and scotorefractory males held on short and long daylengths, but were relatively low in females held on short daylengths and especially high in scotorefractory females held on long daylengths.

The plasma concentrations of both cortisol and insulin varied throughout the day in many of the groups tested. However, the variations were not equivalent. The circadian variations of cortisol were similar irrespective of sex, seasonal condition and daylength. Peak concentrations generally occurred about 12 hr after light onset. In contrast, the circadian variations of insulin differed markedly. For example in male hamsters, robust daily variations were found in scotosensitive hamsters held on short daylengths but not on long daylengths and in scotorefractory hamsters held on long daylengths but not on short daylengths. Furthermore, the daily peak occurred during the light in the scotosensitive hamsters and during the dark in the scotorefractory animals. Neither the daily feeding pattern (about 60% consumed during dark) nor the daily variations of glucose concentration varied appreciably with seasonal condition or daylength. They do not appear to determine nor directly reflect the variations in cortisol and glucose concentrations. It is postulated that the daily rhythms of cortisol and insulin are regulated by different neural pacemaker systems and that changes in the phase relations of circadian systems account in part for seasonal changes in body fat stores.     

Early life experiences affect adult delayed-type hypersensitivity in short and long photoperiods

Environmental experiences during development provide animals with important information about future conditions. Siberian hamsters are photoperiodic rodents that dramatically adjust their physiology and behavior to adapt to seasonal changes. For example, during short winter-like days, hamsters enhance some components of immune function putatively to cope with increasing environmental challenges. Furthermore, early life stress alters the developmental course of the immune system. Overall, immune function is typically suppressed in response to chronic stress, but responses vary depending on the type of stress and components of immune function assessed. This led us to hypothesize that delayed-type hypersensitivity (DTH), an antigen-specific, cell-mediated immune response, would be differentially modulated in hamsters that underwent early life maternal separation (MS) in either short or long photoperiods. At birth, hamsters were assigned to either short (SD; 8 h light/day) or long (LD; 16 h light/day) photoperiods and either daily 3 h MS, daily 15-min brief maternal separation (BMS), or no manipulation from postnatal day 2 through 14. In adulthood DTH was assessed. Hamsters reared in short days enhanced DTH responses. MS and BMS attenuated DTH responses in both short and long days. However, BMS long-day female hamsters did not suppress pinna swelling, suggesting a protective effect of female sex steroids on immune function. As is typical in short days, reproductive tissue was regressed. Reproductive tissue mass was also decreased in long-day MS female hamsters. Furthermore, MS altered photoperiod-induced changes in body mass. Taken together, these findings suggest that manipulations of early life mother-pup interactions in Siberian hamsters result in physiological changes and suppressed cell-mediated immunity.     

Hydroalcoholic Extract of Rabbiteye Blueberry (Vaccinium ashei) Leaves Mitigates Unpredictable Chronic Mild Stress Model Inducing Depressive-Like Behavior in Rats

Several studies reported that rabbiteye blueberry (Vaccinium ashei Reade) leaves present promising biological properties. To the best of our knowledge, no study investigated the possible application of their hydroalcoholic extract for treating mood disorders. Herein, we evaluated if the hydroalcoholic extract of rabbiteye blueberry (Vaccinium ashei Reade) leaves (HEV) promotes an antidepressant-like effect in rodents using chronic experimental approaches. The effect of repeated administration of HEV (50 mg/kg, p.o.) on the immobility time was assessed in the forced swimming test (FST) in an unpredictable chronic mild stress (UCMS) model. Repeated treatment with HEV reversed the depressive-like behavior induced by UCMS by reducing the immobility time. Besides, the exposure to HEV caused no changes in relative organ weights in rats submitted to UCMS. The results indicated that HEV administration presented antidepressant-like action devoid of toxic effects. Thus, it is possible to suggest its potential as a safe and accessible therapeutic tool in the management of depression and other related mood disorders.     

Stress-Induced Anxiety- and Depressive-Like Phenotype Associated with Transient Reduction in Neurogenesis in Adult Nestin-CreERT2/Diphtheria Toxin Fragment A Transgenic Mice

Depression and anxiety involve hippocampal dysfunction, but the specific relationship between these mood disorders and adult hippocampal dentate gyrus neurogenesis remains unclear. In both humans with MDD and rodent models of depression, administration of antidepressants increases DG progenitor and granule cell number, yet rodents with induced ablation of DG neurogenesis typically do not demonstrate depressive- or anxiety-like behaviors. The conflicting data may be explained by the varied duration and degree to which adult neurogenesis is reduced in different rodent neurogenesis ablation models. In order to test this hypothesis we examined how a transient–rather than permanent–inducible reduction in neurogenesis would alter depressive- and anxiety-like behaviors. Transgenic Nestin-CreER^T2/floxed diphtheria toxin fragment A (DTA) mice (Cre+DTA+) and littermates (Cre+DTA-; control) were given tamoxifen (TAM) to induce recombination and decrease nestin-expressing stem cells and their progeny. The decreased neurogenesis was transient: 12 days post-TAM Cre+DTA+ mice had fewer DG proliferating Ki67+ cells and fewer DCX+ neuroblasts/immature neurons relative to control, but 30 days post-TAM Cre+DTA+ mice had the same DCX+ cell number as control. This ability of DG neurogenesis to recover after partial ablation also correlated with changes in behavior. Relative to control, Cre+DTA+ mice tested between 12–30 days post-TAM displayed indices of a stress-induced anxiety phenotype–longer latency to consume highly palatable food in the unfamiliar cage in the novelty-induced hypophagia test, and a depression phenotype–longer time of immobility in the tail suspension test, but Cre+DTA+ mice tested after 30 days post-TAM did not. These findings suggest a functional association between adult neurogenesis and stress induced anxiety- and depressive-like behaviors, where induced reduction in DCX+ cells at the time of behavioral testing is coupled with stress-induced anxiety and a depressive phenotype, and recovery of DCX+ cell number corresponds to normalization of these behaviors.