Stress-induced Memory Impairment Research Articles

ADRA2B genotype modulates effects of acute psychosocial stress on emotional memory retrieval in healthy young men

Previous studies have shown that acute psychosocial stress impairs retrieval of declarative memory with emotional material being especially sensitive to this effect. A functional deletion variant of the ADRA2B gene encoding the α2B-adrenergic receptor has been shown to increase emotional memory and neural activity in the amygdala. We investigated the effects of acute psychosocial stress and the ADRA2B allele on recognition memory for emotional and neutral faces. Fourty-two healthy, non-smoker male volunteers (30 deletion carriers, 12 noncarriers) were tested with a face recognition paradigm. During encoding they were presented with emotional and neutral faces. One hour later, participants underwent either a stress (“Trier Social Stress Test (TSST)”) or a control procedure which was followed immediately by the retrieval session where subjects had to indicate whether the presented face was old or new. Stress increased salivary cortisol concentrations, blood pressure and pulse and impaired recognition memory for faces independent of emotional valence and genotype. Participants showed generally slower reaction times to emotional faces. Carriers of the ADRA2B functional deletion variant showed an impaired recognition and slower retrieval of neutral faces under stress. Further, they were significantly slower in retrieving fearful faces in the control condition. The findings indicate that a genetic variation of the noradrenergic system may preserve emotional faces from stress-induced memory impairments seen for neutral faces and heighten reactivity to emotional stimuli under control conditions.

Alcohol administration blocks stress-induced impairments in memory and anxiety, and alters hippocampal neurotransmitter receptor expression in male rats

Chronic exposure to stress has many deleterious effects on behavior, which can often lead to self-medication with anxiolytics, antidepressants, or alcohol. We determined the effects of alcohol administration following a stressor on established behavioral, physiological, and neural responses to stress. Male Sprague–Dawley rats received: No alcohol/No stress (CON), Alcohol alone (ALC), Stress alone (STR), or Stress plus Alcohol (STR+ALC). For seven consecutive days, two cohorts received an oral dose of 2.0g/kg of either 20% ethanol or saline. In Cohort 1, behavioral testing began after the final treatment (day-8). Memory was tested using the object recognition (OR) and Y-maze, anxiety on the plus maze, and depression on the forced swim task. Memory on OR and Y-maze tasks was impaired in the ALC and STR groups. This deficit was reversed in the STR+ALC group, which performed not differently from the CON group. Stress alone was associated with increased anxiety, which was alleviated with alcohol treatment. No treatment effects were found in the forced swim task. In Cohort 2, hippocampal GABAα4 was upregulated in the STR+ALC group and GluN2B was upregulated in the ALC and STR+ALC groups. The STR+ALC group in Cohort 1 showed enhanced corticosterone levels after forced swim. The STR+ALC group in Cohort 2 showed increased corticosterone levels on day-1 of treatment and a habituation by day-7. In conclusion, this study found a reversal of stress-induced deficits in cognition and anxiety when alcohol was given post-stress, and changes in neurotransmitter receptor expression may contribute to these behavioral effects.

The interaction of chronic restraint stress and voluntary alcohol intake: Effects on spatial memory in male rats

Alcohol consumption and exposure to stressful life events activate similar neural pathways and thus result in several comparable physiological and behavioral effects. Alcoholics in treatment claim that life stressors are the leading cause of continued drinking or relapse. However, few studies have investigated the interactive effects of stress and alcohol on cognitive behavior. The effects of restraint stress, alcohol, and stress in combination with alcohol were examined on a spatial memory test, the object placement (OP) task. In addition, intake levels were measured to determine if stress altered general consumption of alcohol. Male Sprague-Dawley rats were assigned to one of four conditions: no alcohol/no stress control (CON), stress alone (STR), alcohol alone (ALC), and STR+alcohol (STR+ALC). Following each restraint stress bout, the STR+ALC and the ALC groups were given access to 8% alcohol for 1h using the two-bottle choice limited access paradigm. As predicted, the STR+ALC group significantly increased alcohol consumption, while the ALC group had consistent drinking over the 10-day treatment. On the OP task, STR and ALC groups performed at chance levels, whereas the CON and STR+ALC groups significantly discriminated between objects in the new and old locations. These data show that stress increases alcohol intake and the intake of alcohol is associated with reduction of the stress-induced impairment of spatial memory. The data have important implications for the development of alcohol abuse and its treatment.

Chewing ameliorates stress-induced suppression of spatial memory by increasing glucocorticoid receptor expression in the hippocampus

Chewing alters hypothalamic–pituitary–adrenal axis function and improves the ability to cope with stress in rodents. Given that stress negatively influences hippocampus-dependent learning and memory, we aimed to elucidate whether masticatory movements, namely chewing, improve the stress-induced impairment of spatial memory in conjunction with increased hippocampal glucocorticoid receptor expression. Male Sprague–Dawley rats were subjected to restraint stress by immobilization for 2h: the stress with chewing (SC) group were allowed to chew on a wooden stick during the latter half of the immobilization period, whereas the stress without chewing (ST) group were not allowed to do so. Performance in the Morris water maze test was significantly impaired in the ST group compared with the SC group. Further, the numbers of glucocorticoid receptor immunopositive neurons in the hippocampal cornu ammonis 1 region were significantly lower in the ST group than in the control and SC groups. The control and SC rats showed no significant differences in both the water maze performance and the numbers of glucocorticoid receptor-immunopositive neurons. The immunohistochemical finding correlated with the performance in the water maze test. These results suggest that chewing is a behavioral mechanism to cope with stress by increasing hippocampal glucocorticoid receptor expression.

Nardostachys jatamansi extract prevents chronic restraint stress-induced learning and memory deficits in a radial arm maze task

Nardostachys jatamansi is traditionally used in alternative medicine for treatment of neuropsychiatric disorders. We investigated the potential of N. jatamansi extract (NJE) in protecting against chronic stress-induced impairments in spatial learning and memory. The rats were exposed to 21 days of chronic restraint stress and simultaneously received 100 mg or 200 mg/kg body weight of NJE following which acquisition and retention of hippocampus-dependent spatial memory were tested in a partially-baited eight arm radial maze. Animals treated with 200 mg/kg body weight NJE had learning curves comparable to control unstressed animals, made significantly more correct choices (38%, P < 0.001), and fewer reference memory errors (53%, P < 0.01) on the eighth day of training compared to untreated stressed animals as well as stressed animals which received vehicle or a lower dose (100 mg/kg) of NJE. NJE-treated animals also made significantly higher correct choices (31%, P < 0.001) than untreated animals in a retention test 10 days after the training period. We propose that NJE has a protective effect of stress-induced impairments in hippocampus-dependent learning and memory behavior in rats.

Influence of Gut Microbes on the Brain-Gut Axis (Gut 2011;60:307-317)

Psychological stress and its morbidity are often encountered in functional gut disorders and this emphasizes the importance of the brain-gut axis in regulating gastrointestinal physiology.1,2 The bidirectional interaction between the gut and the brain is vital in maintaining homeostasis but the exact mechanism on how both communicate remains elusive. Evidence from animal studies suggests a possible role of intestinal microbiota to influence central control in this brain-gut axis.3,4 The current study by Gareau et al5 in the Gut 2011 issue provided a direct link for the first time between enteric infection and impaired learning and memory in the presence of psychological stress. The memory impairment persisted even after bacterial clearance and resolution of intestinal pathology. In addition, the study demonstrated the beneficial effect of probiotics in preventing stress-induced memory deficits, normalizing alteration in the hypothalamic-pituitary-adrenal (HPA) axis and colonic injury. This effect was associated, in part, with the restoration of hippocampus brain-derived neurotropic factor (BDNF) and c-Fos expression in the context of normalized microbiota. Germ-free mice also displayed an absence of memory, providing support for the requirement of commensal gut microbiota in memory. In this study, female mice at 5-6 weeks were sourced commercially from 2 sites (Charles River, Canada and Taconic Farms, New York, USA) but both populations of mice behaved similarly according to the author (data not shown). Germ-free mice were contained for 72-96 hours before study to normalize the stress from shipping. The mice were infected with Citrobacter rodentium (strain DBS100, Dr David Schauer, Massachusetts Institute of Technology, MA, USA) administered by oral gavage and were tested for behavior at 10 days and 30 days after infection, respectively.6 C. rodentium is a gram-negative bacterium that causes transient colitis in mice including attaching and effacing lesions and colonic epithelial cell hyperplasia.7 A subset of mice was treated with probiotics (Lacidofil, Montreal, Canada) or placebo daily via their drinking water (orogastric gavage induces stress) starting 1 week before infection. Psychological stress was induced using water avoidance stress,8 behavioral testing included the novel object test,9 while the T-maze test10 was used for dorsal hippocampus memory function (non-spatial and working memory) and light/dark box test11 for anxiety. After behavioral testing, the mice were sacrificed. Blood was collected for serum corticosterone to measure HPA activation, colon tissue for histology to assess for colonic pathology, intra-colonic fecal samples for assessment of bacterial DNA and brain tissue to assess for intensity of BDNF and c-Fos in the CA1 region of the hippocampus. C.rodentium infection in mice was not associated with anxiety behavior whether stressed or not. This was in contrast with another study showing an anxiety response after 8 hours of infection.12 However the current study assessed for anxiety after 10 days which was at the peak of host response to the pathogen. Infected mice demonstrated water avoidance stress-induced memory impairment which was maintained until 30 days after infection, a time period where bacteria should clear and colonic lesions resolved. Probiotics when administered to mice, prevented stress-induced memory deficits with reduction in hippocampus BDNF and c-Fos, reduced serum corticosterone, ameliorated colonic injuries and normalized changes in intestinal microbiota. To confirm the role of microbiota in mediating memory, behavior was studied in germ-free mice. No anxiety was observed in the germ-free mice but memory deficits were evident and this was associated with decrease in hippocampus BDNF and c-Fos.

Membrane Mineralocorticoid but not Glucocorticoid Receptors of the Dorsal Hippocampus Mediate the Rapid Effects of Corticosterone on Memory Retrieval

This study was aimed at determining the type of the glucocorticoid membrane receptors (mineralocorticoid receptors (MRs) or glucocorticoid receptors (GRs)) in the dorsal hippocampus (dHPC) involved in the rapid effects of corticosterone or stress on memory retrieval. For that purpose, we synthesized corticosterone–3-O-carboxymethyloxime–bovine serum albumin conjugate (Cort–3CMO–BSA) conjugate (a high MW complex that cannot cross the cell membrane) totally devoid of free corticosterone, stable in physiological conditions. In a first experiment, we evidenced that an acute stress (electric footshocks) induced both a dHPC corticosterone rise measured by microdialysis and memory retrieval impairment on delayed alternation task. Both the endocrinal and cognitive effects of stress were blocked by metyrapone (a corticosterone synthesis inhibitor). In a second experiment, we showed that bilateral injections of either corticosterone or Cort–3CMO–BSA in dHPC 15 min before memory testing produced impairments similar to those resulting from acute stress. Furthermore, we showed that anisomycin (a protein synthesis inhibitor) failed to block the deleterious effect of Cort–3CMO–BSA on memory. In a third experiment, we evidenced that intra-hippocampal injection of RU-28318 (MR antagonist) but not of RU-38486 (GR antagonist) totally blocked the Cort–3CMO–BSA-induced memory retrieval deficit. In a fourth experiment, we demonstrated that RU-28318 administered 15 min before stress blocked the stress-induced memory impairments when behavioral testing occurred 15 min but not 60 min after stress. Overall, this study provides strong in vivo evidence that the dHPC membrane GRs, mediating the rapid and non-genomic effects of acute stress on memory retrieval, are of MR but not GR type.

Systemic opioid receptor antagonism blocks swim stress-induced retention impairment independently from CA1 and BLA opioidergic pathways

Aims The basolateral amygdale (BLA) and dorsal hippocampus (CA1) are critical sites in mediating the effects of stress hormones on memory formation. Severe stress exposure induces memory impairment probably through activating inhibitory modulatory mechanisms such as opioidergic pathways. However, the detailed mechanisms and effect sites are not well understood. The present study was designed to investigate whether opioidergic agents, specifically in the BLA and CA1, are implicated in memory impairment induced by stressful situations. Main methods Rats carrying bilateral cannulae aimed at the BLA or CA1 were trained in a step-through passive-avoidance task and immediately were exposed to a forced swim (SW) stress (10 min, 20 °C). Retention was assessed 24 h after the training session after the animals had received a systemic or microinjection of naltrexone (a classical opioid antagonist) into the BLA/CA1 before training. Key findings The systemic administration of naltrexone (0.5, 1.5, and 3 mg/kg) blocked SW stress-induced memory impairment in a dose-dependent manner, while the microinjection into the BLA (5, 10, and 20 μg/rat) or CA1 (5, 10, and 20 μg/site) exhibited no effect on the disruptive pattern. Significance These findings, albeit confirming the role of opioidergic agents in stress-induced memory impairment, rule out the involvement of the BLA and CA1 in this effect. Future studies are needed to evaluate the opioidergic sites which mediate the disruptive effects of stress exposure on memory formation.

Milk-based phospholipids increase morning cortisol availability and improve memory in chronically stressed men

Phospholipids (PLs) have been shown to dampen the activity and reactivity of the hypothalamic-pituitary-adrenal axis (HPAA). To further investigate stress protective effects of PL, 75 chronically stressed men aged 30 to 51 years were enrolled in a randomized and placebo-controlled trial. The subjects received a bovine milk drink with either 0.5% PL, 1% PL, or a placebo for 42 days to test the hypothesis that supplementation with specific phospholipids would normalize the cortisol response of the HPAA. For determining HPAA activity, the cortisol awakening response was studied before and after treatment. In addition, participants were exposed to an acute stressor, the Trier Social Stress Test, to assess treatment effects on stress reactivity and stress-related memory impairment. After receiving PL-enriched milk, both PL groups showed a delayed decline from peak levels in morning salivary cortisol, suggesting a prolonged availability of free cortisol. Treatment with 0.5% PL additionally resulted in a stronger increase of cortisol after awakening, whereas no such differences could be observed in the 1% PL group and the placebo group, respectively. The acute stress response did not significantly differ among placebo and PL groups. An exploratory data analysis further revealed that elderly participants receiving the higher PL dosage had a significant better memory performance after the Trier Social Stress Test as compared with elderly participants from the placebo and low-PL dosage group; no such difference was observed at baseline. Our results suggest that PL may increase the availability of cortisol in chronically stressed men and may attenuate stress-induced memory impairments. Results of the present study are discussed within the context of previous research and current state of knowledge.

P.1.017 Chronic stress-induced impairment of memory in rats can be prevented by parallel administration of cod liver oil

Background: Preclinical evidence indicates that exposure to cocaine influences the activity of the serotonin transporter (5-HTT) as well as several 5-HT receptor subtypes. However, little is known about the relationship between the 5-HTT and 5-HT receptors following cocaine exposure in humans. Objective: We examined the relationship between platelet 5-HTT, a presynaptic 5-HT measure, and prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a postsynaptic 5-HT receptor agonist in cocaine dependent individuals. Methods: Platelet [3H] paroxetine binding sites were assayed and the m-CPP challenge test was performed in 35 African American cocaine dependent individuals and 33 controls. Clinical measures included assessments of drug use severity and depression. Results: Cocaine subjects showed reduced Bmax of [3H] paroxetine (t = 4.67, p < 0.01) and blunted PRL response to m-CPP (F = 21.86, p < 0.01) compared to controls. There was a positive correlation between Bmax and delta PRL [peak − baseline PRL] in cocaine subjects (r = 0.50, p < 0.01) but not in controls (r = 0.19). ANCOVA analyses showed that the cocaine subgroup with moderate and severe reduction in Bmax showed a greater blunting in PRL response compared to the subgroup with mild Bmax reductions (F = 9.44, p < .005). Multivariate regression models showed that the main effects as well as the interaction of Bmax and severity of cocaine use significantly contributed to impaired PRL response (F = 17.90, p < .001). Conclusions: Disturbances in serotonin transporter binding and post-synaptic 5-HT receptor function seem to be associated in cocaine-dependent subjects. Severity of cocaine use appears to mediate this relationship. Whether there is a causal association between the two measures, or cocaine has separate and independent pre- and post-synaptic effects needs to be clarified.

Ascorbic Acid Protects Against Restraint Stress-Induced Memory Deficits in Wistar Rats

OBJECTIVE:Chronic stress has been shown to cause oxidative damage in the central nervous system. Although stress-induced impairments in learning and memory have been studied extensively, very few studies have investigated possible ways to prevent their ill effects. The present work was designed to study the protective effects of ascorbic acid in memory loss induced by chronic restraint stress.METHODS:Adult male Wistar rats were designated into the following groups: (i) Normal control, (ii) Ascorbic acid treatment, (iii) Vehicle control, (iv) Restraint stress, (v) Restraint stress + vehicle, and (vi) Restraint stress + ascorbic acid treatment. At the end of 21 days, animals of all groups were subjected to memory tests using Morris water maze and passive avoidance apparatus. Then, the results obtained were compared between the experimental groups.RESULTS:Rats exposed to restraint stress alone and those pretreated with vehicle solution before restrained stress showed deficits in learning and impaired memory retention in the memory tests when compared to animals in other experimental groups. Animals pretreated with ascorbic acid before restraining showed significant improvement in memory retention in the same memory tests.CONCLUSIONS:Results of this study suggest the possibility of using ascorbic acid as a dietary supplement to prevent stress-induced memory impairments.

Central noradrenergic depletion by DSP-4 prevents stress-induced memory impairments in the object recognition task

Environmental stress produces adverse affects on memory in humans and rodents. Increased noradrenergic neurotransmission is a major component of the response to stress and noradrenaline (NA) plays an important role in modulating processes involved in learning and memory. The present study investigated the effect of NA depletion on stress-induced changes on memory performance in the mouse. Central NA depletion was induced using the selective neurotoxin N-(2-chloroethyl)- N-ethyl-2 bromobenzylamine (DSP-4) and verified by high performance liquid chromatography (HPLC). A novel cage stress procedure involving exposure to a new clean cage for 1 h per day, 4 days per week for 4 weeks, was used to produce stress-induced memory deficits measured using the object recognition task. 50 mg/kg DSP-4 produced large and sustained reductions in NA levels in the frontal cortex and hippocampus measured 24 h, 1 week and 5 weeks after treatment. Four weeks of exposure to novel cage stress induced a memory deficit in the object recognition task which was prevented by DSP-4 pre-treatment (50 mg/kg 1 week before the commencement of stress).These findings indicate that chronic environmental stress adversely affects recognition memory and that this effect is, in part, mediated by the noradrenergic stress response. The implication of these findings is that drugs targeting the noradrenergic system to reduce over-activity may be beneficial in the treatment of stress-related mental disorders such as post-traumatic stress disorder or anxiety in which memory is affected.

Oral supplementation with melon superoxide dismutase extract promotes antioxidant defences in the brain and prevents stress-induced impairment of spatial memory

The purpose of this study was to investigate the effect of antioxidant ingestion on stress-induced impairment of cognitive memory. Male C57BL/6 mice were divided into four groups as follows: (1) control mice (C mice) fed in a normal cage without immobilization; (2) restraint-stressed (RS mice) fed in a small cage; (3) vitamin E mice (VE mice), mice were fed in a small cage with a diet supplemented with vitamin E; (4) GliSODin mice (GS mice) fed in a small cage with a diet supplemented with GliSODin. RS, VE and GS mice were exposed to 12 h of immobilization daily. Five weeks later, spatial learning was measured using the Morris Water Maze (MWM) test. After water maze testing, we performed immunohistochemical analysis using 4-hydroxy-2-noneral (4-HNE) and an anti-Ki67 antibody. 4-HNE is a marker of lipid peroxidation. RS mice showed impaired spatial learning performance and an increased number of 4-HNE-positive cells in the granule cell layer (GCL) of the hippocampal dentate gyrus when compared to C mice. Moreover, RS mice showed a decreased number of Ki67-positive cells in the subgranular zone (SGZ). GS mice showed better spatial learning memory than RS mice. The number of 4-HNE-positive cells in the GCL of GS mice was significantly less than that of RS mice. The number of Ki67-positive cells in the SGZ of GS mice was significantly greater than that of RS mice. These finding suggests that GliSODin prevents stress-induced impairment of cognitive function and maintains neurogenesis in the hippocampus through antioxidant activity.

Effect of &lt;i&gt;Bupleurum falcatum&lt;/i&gt; on the Stress-Induced Impairment of Spatial Working Memory in Rats

Many studies have shown that Bupleurum falcatum (BF), which is widely used in the treatment of various psychosomatic diseases in traditional Oriental medicine, is an effective therapeutic intervention for memory impairment. The purpose of this study was to examine the effect of BF on stress-induced alterations in learning and memory in rats using the Morris water maze (MWM) and elevated plus maze (EPM) behavioral tests. In addition, we examined the effects of BF treatment on the cholinergic system, as indicated by changes in neuronal choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) immunoreactivity in the hippocampus. BF (150, 300, or 600 mg/kg) was administered orally 30 min before exposure to repeated immobilization (IMO) stress (4 h/d for 14 d). The BF treatment produced a significant improvement in escape latency (time required to find the platform) in the MWM, and it also produced an anxiolytic-like effect in the EPM. Consistent with the behavioral data, BF treatment significantly attenuated the IMO stress-induced loss of cholinergic immunoreactivity in the hippocampus. These findings indicate that BF has a protective effect against repeated IMO stress-induced neuronal and cognitive impairments, and they suggest that BF may be useful in the treatment of stress-induced memory impairment.

Tianeptine: An Antidepressant with Memory-Protective Properties

The development of effective pharmacotherapy for major depression is important because it is such a widespread and debilitating mental disorder. Here, we have reviewed preclinical and clinical studies on tianeptine, an atypical antidepressant which ameliorates the adverse effects of stress on brain and memory. In animal studies, tianeptine has been shown to prevent stress-induced morphological sequelae in the hippocampus and amygdala, as well as to prevent stress from impairing synaptic plasticity in the prefrontal cortex and hippocampus. Tianeptine also has memory-protective characteristics, as it blocks the adverse effects of stress on hippocampus-dependent learning and memory. We have further extended the findings on stress, memory and tianeptine here with two novel observations: 1) stress impairs spatial memory in adrenalectomized (ADX), thereby corticosterone-depleted, rats; and 2) the stress-induced impairment of memory in ADX rats is blocked by tianeptine. These findings are consistent with previous research which indicates that tianeptine produces anti-stress and memory-protective properties without altering the response of the hypothalamic-pituitary-adrenal axis to stress. We conclude with a discussion of findings which indicate that tianeptine accomplishes its anti-stress effects by normalizing stress-induced increases in glutamate in the hippocampus and amygdala. This finding is potentially relevant to recent research which indicates that abnormalities in glutamatergic neurotransmission are involved in the pathogenesis of depression. Ultimately, tianeptine’s prevention of depression-induced sequelae in the brain is likely to be a primary factor in its effectiveness as a pharmacological treatment for depression.

BT‐11 improves stress‐induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains

In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to be an important herb that exhibits sedative effects in insomnia, palpitation with anxiety, restlessness, and disorientation in humans. We previously reported that BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed that BT-11 could remedy stress-induced memory deficits in rats. In this study, the stress-induced memory impairments in rats were significantly reversed almost to the control level by BT-11 treatment. To seek an active component of BT-11 that plays an important role in antipsychotic effects, we compared BT-11 with 3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root extracts. However, the effects of TMCA were less or were not consistent with those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the levels of neural cell adhesion molecule (NCAM) in rat brains to the control levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory impairments through increment of glucose utilization and total NCAM levels in rat brains. In conclusion, BT-11 may be strongly effective against stress-induced amnesia in rats, through the combined effects of TMCA and other active components of BT-11.

The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats

Agomelatine, a novel antidepressant with established clinical efficacy, acts as a melatonin receptor agonist and 5-HT(2C) receptor antagonist. As stress is a significant risk factor in the development of depression, we sought to determine if chronic agomelatine treatment would block the stress-induced impairment of memory in rats trained in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. Moreover, since neural cell adhesion molecule (NCAM) is known to be critically involved in memory consolidation and synaptic plasticity, we evaluated the effects of agomelatine on NCAM, and polysialylated NCAM (PSA-NCAM) expression in rats given spatial memory training with or without predator stress. Adult male rats were pre-treated with agomelatine (10 mg/kg i.p., daily for 22 d), followed by a single day of RAWM training and memory testing. Rats were given 12 training trials and then they were placed either in their home cages (no stress) or near a cat (predator stress). Thirty minutes later the rats were given a memory test trial followed immediately by brain extraction. We found that: (1) agomelatine blocked the predator stress-induced impairment of spatial memory; (2) agomelatine-treated stressed, as well as non-stressed, rats exhibited a rapid training-induced increase in the expression of synaptic NCAM in the ventral hippocampus; and (3) agomelatine treatment blocked the water-maze training-induced decrease in PSA-NCAM levels in both stressed and non-stressed animals. This work provides novel observations which indicate that agomelatine blocks the adverse effects of stress on hippocampus-dependent memory and activates molecular mechanisms of memory storage in response to a learning experience.

Increased dopaminergic signaling impairs aversive olfactory memory retention in Drosophila

Dopamine is necessary for the aversive olfactory associative memory formation in Drosophila, but its effect on other stages of memory is not known. Herein, we studied the effect of enhanced dopaminergic signaling on aversive olfactory memory retention in flies. We used l-3,4-dihydroxyphenylalanine ( l-DOPA) to elevate dopamine levels: l-DOPA-treated flies exhibited a normal learning performance, but a decrease in 1-h memory. Dopamine transporter (DAT) mutant flies or flies treated with the DAT inhibitor desipramine exhibited poor memory retention. Flies subjected to heat stress after training exhibited a decrease in memory. Memory was restored by blocking dopaminergic neuronal output during heat stress, suggesting that dopamine is involved in heat stress-induced memory impairment in flies. Taken together, our findings suggest that increased dopaminergic signaling impairs aversive olfactory memory retention in flies.

Viral vector-mediated blockade of the endocrine stress–response modulates non-spatial memory

Stress results in the release of glucocorticoids (GCs) which at high levels, impair performance on hippocampus-dependent tasks. Estrogen is neurotrophic and can rescue stress-induced memory impairments. Here we report the use of a viral vector to overexpress a chimeric gene (ER/GR) that converts the deleterious effects of glucocorticoids into beneficial estrogenic effects. A short immobilization stress regimen was sufficient to impair non-spatial memory. In contrast, viral vector-mediated overexpression of ER/GR in the dentate gyrus of the hippocampus protected against stress-induced impairments of non-spatial memory. These data add to the growing evidence that increasing estrogenic signaling can protect against the impairing effects of stress on non-spatial memory.

Protective effect of physical exercise on stress-induced impairment of spatial memory is dependent on IGF-1

Protective effect of physical exercise on stress-induced impairment of spatial memory is dependent on IGF-1