Recognition memory in tree shrew (Tupaia belangeri) after repeated familiarization sessions

Recognition memories are formed during perceptual experience and allow subsequent recognition of previously encountered objects as well as their distinction from novel objects. As a consequence, novel objects are generally explored longer than familiar objects by many species. This novelty preference has been documented in rodents using the novel object recognition (NOR) test, as well is in primates including humans using preferential looking time paradigms. Here, we examine novelty preference using the NOR task in tree shrew, a small animal species that is considered to be an intermediary between rodents and primates. Our paradigm consisted of three phases: arena familiarization, object familiarization sessions with two identical objects in the arena and finally a test session following a 24-h retention period with a familiar and a novel object in the arena. We employed two different object familiarization durations: one and three sessions on consecutive days. After three object familiarization sessions, tree shrews exhibited robust preference for novel objects on the test day. This was accompanied by significant reduction in familiar object exploration time, occurring largely between the first and second day of object familiarization. By contrast, tree shrews did not show a significant preference for the novel object after a one-session object familiarization. Nonetheless, they spent significantly less time exploring the familiar object on the test day compared to the object familiarization day, indicating that they did maintain a memory trace for the familiar object. Our study revealed different time courses for familiar object habituation and emergence of novelty preference, suggesting that novelty preference is dependent on well-consolidated memory of the competing familiar object. Taken together, our results demonstrate robust novelty preference of tree shrews, in general similarity to previous findings in rodents and primates.     

Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory

Damage to the hippocampus (HPC) using the excitotoxin N-methyl-D-aspartate (NMDA) can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity) during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA-induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX), a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA-induced, or no damage to the HPC at a recent (24 hours) or remote (5 weeks) time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories.     

The effect of ghrelin on MK-801 induced memory impairment in rats

Accumulating evidence indicates that the brain-gut peptide ghrelin which is expressed in hippocampus improves memory and learning processes. The MK-801, a noncompetitive NMDA receptor antagonist, has also shown amnesic properties in animal model. The current study was to find out whether intracerebroventricular administration of ghrelin can prevent amnesia induced by MK-801 in rats. A week after the surgery, during which cannuals were implanted in the lateral ventricular, the animals were trained and tested in a step-through type passive avoidance task. Memory retrieval was measured by step-through latency (STL) and total time in dark compartments (TDC). In the first series of experiments, we established a dose–response relationship for ghrelin on the passive avoidance paradigm. In the second set of experiments, animals were divided to two groups. In the first group, MK-801 (0.075, 0.15 and 0.3 mg/kg) was injected intraperitoneally (i.p.) immediately after the acquisition session and in the second group MK-801 (same doses) was injected (i.p.) 30 min before the retention session. Analysis of data showed that in both groups, MK-801 impaired learning and memory. In the third set of experiments, administration of ghrelin (200 ng/rat) right after the acquisition session (i.e. before MK-801 injection) improved the MK-801 induced memory impairment, but administration of ghrelin before retrieval session did not affect the MK-801 induced memory impairment.These results show an interaction between ghrelin and glutamatergic system. A novel finding in this study is that ghrelin can prevent amnesia produced by NMDA antagonist in rats when injected in post-training phase.     

Environmental Enrichment Enhances Episodic-Like Memory in Association with a Modified Neuronal Activation Profile in Adult Mice

Although environmental enrichment is well known to improve learning and memory in rodents, the underlying neuronal networks'' plasticity remains poorly described. Modifications of the brain activation pattern by enriched condition (EC), especially in the frontal cortex and the baso-lateral amygdala, have been reported during an aversive memory task in rodents. The aims of our study were to examine 1) whether EC modulates episodic-like memory in an object recognition task and 2) whether EC modulates the task-induced neuronal networks. To this end, adult male mice were housed either in standard condition (SC) or in EC for three weeks before behavioral experiments (n = 12/group). Memory performances were examined in an object recognition task performed in a Y-maze with a 2-hour or 24-hour delay between presentation and test (inter-session intervals, ISI). To characterize the mechanisms underlying the promnesiant effect of EC, the brain activation profile was assessed after either the presentation or the test sessions using immunohistochemical techniques with c-Fos as a neuronal activation marker. EC did not modulate memory performances after a 2 h-ISI, but extended object recognition memory to a 24 h-ISI. In contrast, SC mice did not discriminate the novel object at this ISI. Compared to SC mice, no activation related to the presentation session was found in selected brain regions of EC mice (in particular, no effect was found in the hippocampus and the perirhinal cortex and a reduced activation was found in the baso-lateral amygdala). On the other hand, an activation of the hippocampus and the infralimbic cortex was observed after the test session for EC, but not SC mice. These results suggest that the persistence of object recognition memory in EC could be related to a reorganization of neuronal networks occurring as early as the memory encoding.     

Effects of theanine, a unique amino acid in tea leaves, on memory in a rat behavioral test

We identified an effect of theanine on memory functions in a novel object test. Rats were fed theanine for 3 weeks ad libitum, and then they performed the object test. The theanine-fed group performed search behavior for the novel object in the test session. The results suggest that theanine-fed rats showed improved recognition, and that theanine affected learning and memory.     

The choose-short effect in rat memory for event duration: the subjective-shortening model

Two predictions derived from the subjective-shortening model were tested in rats. The predictions concerned the temporary occurrence of the choose-short effect with extended training at a given retention interval (RI) and the occurrence of a temporary choose-long effect, when RIs shorter than those used during training were applied. In a first experiment, using a stepwise delay procedure with training 0-s RI sessions interpolated between each series of increasing RIs, results showed: (1) a choose-short effect during the stepwise increase in the delay procedure, (2) a temporary occurrence of the choose-short effect during testing at a given RI and (3) a choose-long effect in half of the animals, when a RI shorter than that used previously was applied. These contrasting results suggest that the disappearance of the choose-short effect could be, as proposed by the model, either the consequence of the foreshortening of the reference memory (for rats choosing-long) or the consequence of an adaptation of the working memory (for rats which did not choose long). Results were discussed in relation with the procedure which could have contributed, by the interposition of 0-s RI sessions, to maintain a stable reference memory. In order to test this interpretation, a second experiment, using the classical stepwise delay procedure without training sessions interpolated, was carried out. In these conditions, rats did never present a significant choose-long effect when the RI was shortened. These results suggest that rats maintained a stable reference memory and could improve their performances during retention testing sessions either by an adaptation of their working memory or by the adoption of an alternative strategy which consisted in learning to maintain an orientation towards the location of the correct lever.     

Is "scopolamine-induced amnesia" in rats the result of state-dependent learning?

The effects of a single and repetitive administration of m-cholinoblocker scopolamine (Sc) to male rats on retention of step-through passive avoidance (PA) or active avoidance (AA) in a shuttle-box were compared. In case of PA Sc (1 mg/kg) was injected i.p. only 30 min before training, only 30 min before testing, or both before training and before testing. In case of AA Sc (0.5 mg/kg/day) was injected i.p. only 15 min before each training session or both before training and before testing (44 days after achievement of learning criterion). The PA and AA retention were impaired only in the experiments, where the drug was administered before training, but did not differ from control, when Sc was injected twice. The Sc-induced amnesia (like many other cases of memory deficits) is suggested to be a manifestation of state-dependent learning. Similarity between the brain state during memory consolidation and during the retention test is necessary for recollection.     

Moderate prenatal carbon monoxide exposure produces persistent, and apparently permanent, memory deficits in rats

The effects of moderate (150 +/- 2 ppm) prenatal carbon monoxide (CO) exposure (maternal HbCO concentrations of 15.6 +/- 1.1%) on learning and memory were assessed in young and aged adult rats using a two-way active avoidance paradigm. In experiment 1, the prenatal CO-exposed rats at 120 days of age acquired a conditioned avoidance response equally well as control animals in a 100-trial session. However, following a 24-hr interval the CO-exposed rats failed to demonstrate significant retention of the task as indicated by the absence of significant improvement in performance over the indicated by the absence of significant improvement in performance over the previous day; control subjects did show significant retention. In experiment 2, in which 120-day-old animals received 50 training trials per day until a criterion of ten consecutive avoidance responses was met, the prenatal CO-exposed subjects again acquired the task as well as control animals. When tested for retention 28 days later, a significant memory impairment was again observed in terms of trials required to reattain the avoidance criterion as well as in total percent avoidance responding. In neither experiment did an analysis of initial or average latency to escape the footshock stimulus reveal any significant alterations. These latter results suggest that the observed performance impairment reflected a memory deficit and not a disruption of sensory, motor, or motivational factors. In experiment 3, prenatal CO-exposed rats approximately 1 year of age (300-360 days of age) showed impairment relative to air-exposed controls in both the original learning and retention of the two-way avoidance response. Again, however, there was no evidence for alterations in performance factors per se. Collectively these data indicate that while young adult rats prenatally exposed to 150 ppm CO demonstrate an associative deficit restricted to memory impairment, aged adults similarly exposed during the prenatal period display a more pronounced deficit similar to that recently reported for animals tested as juveniles. The importance of parametric manipulations in uncovering long-term toxicity is also discussed.     

慢性束缚应激对SD和Wistar大鼠学习记忆能力的影响

目的探讨慢性束缚应激对Wistar、SD两种品系大鼠学习记忆能力的影响,为应激模型中实验动物的选择提供依据。方法对两种品系大鼠(Wistar、SD)采用每天束缚10 h,束缚28 d建立慢性应激模型。采用物体认知新物体识别实验和Morris水迷宫空间学习、工作记忆行为学检测方法,观察束缚应激对两种品系实验动物学习记忆能力的影响。结果束缚28 d后,物体识别实验中,Wistar、SD模型组的辨别指数(discrimination index,DI)均低于对照组,但只有SD两组间差异存在显著性(P0.05);水迷宫空间学习阶段,SD模型组潜伏期高于对照组,第5天差异有显著性(P0.05),而Wistar模型组与对照组间的潜伏期没有差异;水迷宫工作记忆阶段,SD大鼠模型组与正常组比较,潜伏期显著增加(P0.05),Wistar模型大鼠的潜伏期与对照组比较没有显著差异。结论新物体识别实验和水迷宫实验,这两种反应动物不同学习记忆能力的行为学实验结果都表明,慢性束缚应激(10 h,28 d)对SD大鼠学习记忆能力的损伤较Wistar大鼠明显。SD大鼠可能更适合作为慢性应激所致学习记忆损伤动物模型。     

Sleep-Effects on Implicit and Explicit Memory in Repeated Visual Search

In repeated visual search tasks, facilitation of reaction times (RTs) due to repetition of the spatial arrangement of items occurs independently of RT facilitation due to improvements in general task performance. Whereas the latter represents typical procedural learning, the former is a kind of implicit memory that depends on the medial temporal lobe (MTL) memory system and is impaired in patients with amnesia. A third type of memory that develops during visual search is the observers’ explicit knowledge of repeated displays. Here, we used a visual search task to investigate whether procedural memory, implicit contextual cueing, and explicit knowledge of repeated configurations, which all arise independently from the same set of stimuli, are influenced by sleep. Observers participated in two experimental sessions, separated by either a nap or a controlled rest period. In each of the two sessions, they performed a visual search task in combination with an explicit recognition task. We found that (1) across sessions, MTL-independent procedural learning was more pronounced for the nap than rest group. This confirms earlier findings, albeit from different motor and perceptual tasks, showing that procedural memory can benefit from sleep. (2) Likewise, the sleep group compared with the rest group showed enhanced context-dependent configural learning in the second session. This is a novel finding, indicating that the MTL-dependent, implicit memory underlying contextual cueing is also sleep-dependent. (3) By contrast, sleep and wake groups displayed equivalent improvements in explicit recognition memory in the second session. Overall, the current study shows that sleep affects MTL-dependent as well as MTL-independent memory, but it affects different, albeit simultaneously acquired, forms of MTL-dependent memory differentially.     

石杉碱甲对电休克大鼠记忆、ARCmRNA及蛋白表达的影响

目的：研究石杉碱甲对电休克模型大鼠记忆和海马活性调节的细胞骨架联合基因（Activity-regulatedcytoskeletal—associatedgene,ARC）表达的影响。方法：大鼠随机分为假电休克对照组和电休克组,再随机分为生理盐水对照组（CS组、ES组）和石杉碱甲组（CH组、EH组）。第l-17天行生理盐水或石杉碱甲灌胃;第8—17天给予假电痉挛刺激或电痉挛刺激;第18天水迷宫定位航线实验;然后各组大鼠随机分成两组,一组取海马用RT．PCR检测ARCmRNA表达,Westem--blot法检测ARC蛋白表达水平,一组于48小时后行水迷宫空间位置探寻实验。结果：电休克导致大鼠显著记忆障碍,ARCmRNA、ARC蛋白表达水平较假电休克对照组显著下降;而石杉碱甲干预的电休克大鼠记忆保持较好,ARCmRNA、ARC蛋白表达水平显著高于生理盐水干预的电休克大鼠,与假电休克大鼠相比无显著性差异。结论：石杉碱甲能减轻电休克模型大鼠记忆损害,其机制可能与海马ARC的表达增加有关。     

Dehydroevodiamine.HCl prevents impairment of learning and memory and neuronal loss in rat models of cognitive disturbance

We previously reported that dehydroevodiamine.HCl (DHED) has anticholinesterase and antiamnesic activities. To verify the effects of DHED on cognitive deficits further, we tested it on the scopolamine-induced amnesia model of the rat using the passive avoidance and eight-arm radial maze tests. A single (20 mg/kg p.o.) and repeated (10 mg/kg p.o.) administrations of DHED could significantly reverse the latency time shortened by scopolamine (1 mg/kg i.p.) to control level. The impaired spatial working memory induced by scopolamine (1 mg/kg i.p.) was also improved significantly by a single injection (6.25 mg/kg i.p.) and repeated administrations of DHED (10 mg/kg p.o.) in the eight-arm radial maze test. In addition, we examined the effects of DHED on the memory impairment and the histological changes of the brain after unilateral electrolytic lesion of the entorhinal cortex (EC) and middle cerebral artery occlusion in rats. The cognitive deficits caused by EC lesion and middle cerebral artery occlusion were improved significantly by repeated administrations of DHED (6.25 mg/kg i.p.) after EC lesion or ischemic insult once a day for 7 days in the passive avoidance test. Histological analysis showed that the neuronal loss in the DHED-treated group was notably reduced in the hippocampal area (CA1) of ischemic rats and in the dentate gyrus and hippocampal area (CA1 and CA3) of EC-lesioned rats compared with the nontreated group. The infarction area was decreased significantly by a single administration of DHED (6.25 mg/kg i.p.) 30 min before ischemic insult for 6 h. These results suggest that DHED might be an effective drug for not only the Alzheimer's disease type, but also the vascular type of dementia.     

Preventive effect of cholecystokinin octapeptide on experimental amnesia in rats

The effect of intracerebroventricular (ICV) administration of cholecystokinin octapeptide (CCK-8) on electroconvulsive shock (ECS)-induced amnesia in passive avoidance response was studied in rats. In normal rats, CCK-8 in doses from 1 ng to 1 microgram had no effect on the response when injected before the training trials, immediately after foot shock or before the first retention test. However, proglumide, a CCK-8 receptor blocker, induced marked amnesia when injected in doses from 0.1 to 10 micrograms before the training trials and in doses of 1 and 10 micrograms before the first retention test, though not subsequent to foot shock. ECS given immediately after the foot shock caused amnesia in the 24 hr and 48 hr retention tests, which could have been prevented by CCK-8 injected in doses of 10 ng to 1 microgram prior to the training trials, of 10 ng to 1 microgram following ECS and of 0.1 and 1 microgram before the first retention test. In addition, the effects of CCK-8 and proglumide became pronounced following chronic ICV infusion, using an osmotic minipump, for 7 days at a dose of 1 ng/day and 10 ng/day, respectively. The amnesia induced by proglumide was not affected by arginine vasopressin (AVP), while AVP in doses of 10 ng and 100 ng given 30 min before the training trials prevented ECS-induced amnesia. The antiamnesic effect of AVP was abolished by simultaneous administration of proglumide. On the other hand, AVP-antiserum produced marked amnesia which could be antagonized by CCK-8. However, the antiamnesic effect of CCK-8 was not suppressed by AVP-antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nerve Growth Factor Differentially Affects Spatial and Recognition Memory in Aged Rats

In rats, object discrimination depends on the integrity of the cholinergic system, thus it could be expected that nerve growth factor (NGF) can improve the behavior in aged subjects. The interactive effect of age and cholinergic improvement was assessed behaviorally in young and aged rats. Animals were injected by infusion of NGF into the lateral ventricles and they were tested in two behavioral tasks: an object-location and an object-recognition task. Spatial and recognition memory were assessed in an open field containing five different objects. Rats were submitted to six consecutive sessions. Both age-groups showed comparable habituation of exploratory response in Session 1–4. Discrimination index (DI) was calculated to assess responses to spatial change in Session 5 and object change in Session 6. Control young and aged rats were able to discriminate between familiar and novel object, however DI was lower in aged rats. Treatment with NGF induced decline of object discrimination in both age-groups. Different results were obtained in spatial displacement test. NGF was able to improve spatial memory in aged rats, but had no effect in young controls. These data confer on NGF potential role in improving spatial but not episodic memory in aged rats.     

昆明小鼠物体识别模型的建立及其在检测化学药物对记忆损伤中的应用

本研究的主要目的是建立昆明小鼠物体识别模型并评价该模型在安全药理学研究中的潜在应用价值。研究了昆明小鼠物体识别记忆随时间而减弱的特性,在训练结束后4h或1h,检测昆明小鼠的物体识别记忆,并评价了东莨胆碱对昆明小鼠物体识别记忆的影响。结果表明:1h间隔组昆明小鼠熟悉期探究物体的时间差和测试期探究物体的时间差存在显著差异(P<0.05),昆明小鼠在训练结束后1h记忆保持良好,可以进行物体识别;东莨胆碱组昆明小鼠熟悉期探究物体的时间差和测试期探究物体的时间差比较(P>0.05),没有显著性差异。因此,东莨胆碱损伤了昆明小鼠的物体识别记忆。用昆明小鼠建立的物体识别模型具有简单、快速、可靠等特点,在安全药理学研究中可用于检测化学药物对记忆的损伤。     

The effects of the distribution of training on learning feedback-assisted cardiac acceleration

In order to test a hypothesis derived from a motor skills learning model of cardiac acceleration control, groups of subjects were given biofeedback training for four sessions to learn cardiac acceleration under four different training schedules: (1) all sessions in one day, (2) daily sessions, (3) sessions every other day, and (4) weekly sessions. Ability to accelerate heart rate both with and without feedback was determined at each session. Also ability to accelerate heart rate without feedback was determined 1 week after the last training session as a measure of retention. Although there was highly significant (p less than.0001) evidence of heart rate control both with and without feedback, there were no differences in degree of control attributable to distribution of training sessions. There was, however, a trend (p less than .10) for subjects trained under the most distributed training schedule (weekly) to show more retention than subjects trained under a less distributed schedule (daily).     

A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease

Previous studies have shown that melatonin is implicated in modulating learning and memory processing. Melatonin also exerts neuroprotective activities against Aβ-induced injury in vitro and in vivo. Neu-P11 (piromelatine, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-oxo-4H-pyran-2-carboxamide) is a novel melatonin (MT1/MT2) receptor agonist and a serotonin 5-HT1A/1D receptor agonist recently developed for the treatment of insomnia. In the present study we firstly investigated whether Neu-P11 and melatonin enhance memory performance in the novel object recognition (NOR) task in rats, and then assessed whether Neu-P11 and melatonin improve neuronal and cognitive impairment in a rat model of Alzheimer' disease (AD) induced by intrahippocampal Aβ_(1–42) injection. The results showed that a single morning or afternoon administration of Neu-P11 enhanced object recognition memory measured at 4 or 24 h after training. Melatonin was effective in the memory facilitating effects only when administered in the afternoon. Further results showed that intrahippocampal Aβ_(1–42) injection resulted in hippocampal cellular loss, as well as decreased learning ability and memory in the Y maze and NOR tasks in rats. Neu-P11 but not melatonin attenuated cellular loss and cognitive impairment in the rat AD model. The current data suggest that Neu-P11 may serve as a novel agent for the treatment of AD.     

Effects of Zizyphus jujube Extract on Memory and Learning Impairment Induced by Bilateral Electric Lesions of the Nucleus Basalis of Meynert in Rat

Alzheimer’s disease (AD) is a common neurodegenerative condition that affects the elderly population. Its primary symptom is memory loss. The memory dysfunction in AD has been associated with cortical cholinergic deficiency and loss of cholinergic neurons of the nucleus basalis of Meynert (NBM). Zizyphus jujube (ZJ) activates choline acetyltransferase and may have beneficial effects in AD patients. This study investigates the effect of ZJ extract in intact rats and in rat model of AD. 49 male Wistar rats were divided into seven equal groups (1—control, without surgery, received water), 2—AD (bilateral NBM lesion, received water), 3 and 4—AD + ZJ (NBM bilateral lesion, received ZJ extract 500 and 1,000 mg/kg b.w. per day for 15 days), 5—sham (surgery: electrode introduced into NBM without lesion, received water), 6 and 7—without surgery and lesion, received ZJ extract—the same as groups 3 and 4). The learning and memory performance were assessed using passive avoidance paradigm, and the memory cognition for spatial learning and memory was evaluated by Morris water maze. In shuttle box test ZJ extract (500 and 1,000 mg) significantly increased step-through latency in AD + ZJ groups compared with AD group. In Morris water maze test (in probe day), both AD + ZJ groups receiving extract (500 and 1,000 mg) demonstrated significant preference for the quadrant in which the platform was located on the preceding day as compared with AD group. Our results suggested that ZJ has repairing effects on memory and behavioral disorders produced by NBM lesion in rats and may have beneficial effects in treatment of AD patients.     

Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 °C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15–E18) nor in young postnatal (P14–P17) rats.     

Caffeine improves adult mice performance in the object recognition task and increases BDNF and TrkB independent on phospho-CREB immunocontent in the hippocampus

Caffeine is one of the most psychostimulants consumed all over the world that usually presents positive effects on cognition. In this study, effects of caffeine on mice performance in the object recognition task were tested in different intertrial intervals. In addition, it was analyzed the effects of caffeine on brain derived neurotrophic factor (BDNF) and its receptor, TrkB, immunocontent to try to establish a connection between the behavioral finding and BDNF, one of the neurotrophins strictly involved in memory and learning process. CF1 mice were treated during 4 consecutive days with saline (0.9g%, i.p.) or caffeine (10mg/kg, i.p., equivalent dose corresponding to 2-3 cups of coffee). Caffeine treatment was interrupted 24h before the object recognition task analysis. In the test session performed 15min after training session, caffeine-treated mice recognized more efficiently both the familiar and the novel object. In the test session performed 90min and 24h after training session, caffeine did not change the time spent in the familiar object but increased the object recognition index, when compared to control group. Western blotting analysis of hippocampus from caffeine-treated mice revealed an increase in BDNF and TrkB immunocontent, compared to their saline-matched controls. Phospho-CREB immunocontent did not change with caffeine treatment. Our results suggest that acute treatment with caffeine improves recognition memory, and this effect may be related to an increase of the BDNF and TrkB immunocontent in the hippocampus.