Spatial Memory In Rats Research Articles

The effects of exogenous testosterone on spatial memory in rats

Abstract Testosterone (T) is known to affect spatial abilities in men and women. Studies focusing on this relationship showed that both endogenous variability of T and administration of exogenous T, altered mental rotation and spatial visualization. Organizational and activational effects of T can be separately identified. The aim of our study was to evaluate the activational effects of exogenous T on spatial memory in male and female rats. T was administered 3 times a week over a two week period in either 1 mg/kg for low testosterone group or 10 mg/kg for high testosterone group. The Morris water maze was performed to assess the rat’s working and reference spatial memory. T and estradiol levels were measured in plasma. Increase in plasma T levels was confirmed in the experimental groups in comparison to the control groups (receiving sterile oil, 3 times a week over a two week period). Low dose T impaired working, but improved reference memory in female rats. In male rats the negative effects of T (both doses) on reference memory were shown. This experiment showed that the activational effects of exogenous testosterone on spatial memory of rats were gender and dose-dependent.

Memory performance and scopolamine: Hypoactivity of the thalamus revealed by cytochrome oxidase histochemistry

Spatial memory learning is related to the functioning of a neuronal circuit composed of cortical, hippocampal and diencephalic brain regions. The Morris water maze (MWM) is frequently used to assess spatial memory in rats. In this study, the neuronal functional activity of some brain limbic system regions after a memory task in adult male Wistar rats injected with scopolamine (1.0 mg/kg, i.p.) was assessed using cytochrome oxidase (COx) histochemistry. The rats were trained following a working memory schedule in the MWM. A trained group injected with saline and an untreated control group were examined to compare changes in COx activity in the dorsal hippocampus, anterior thalamus, mammillary nuclei, prefrontal cortex and ventral tegmental area. The scopolamine-treated group showed an impairment of spatial learning. Also, a decrease in COx activity was found in this group as compared to the saline group in the anteroventral and anteromedial thalamic nuclei. Overall, these findings suggest that memory deficits induced by scopolamine may be due to impairment of the cholinergic function in the anterior thalamic nuclei.

Spatial memory: A Rosetta stone for rat and human hippocampal discourse: Theoretical comment on Goodrich-Hunsaker and Hopkins (2010).

The article by Goodrich-Hunsaker and Hopkins (2010, this issue) takes up an important place among in the recent contributions on the role of the hippocampus in memory. They evaluate the effect of bilateral damage to the hippocampus on performance by human participants in a virtual 8-arm radial maze. The hippocampal damage appears to be highly selective and nearly complete. Exactly as with selective hippocampal damage in rats, the human participants showed a deficit in accurately choosing rewarded versus never-rewarded arms and a deficit in avoiding reentering recently visited arms. The results are triply significant: (1) They provide good support for the idea that the wealth of neurobiological information, from network to synapse to gene, on spatial memory in the rat may apply as a whole to the human hippocampal memory system; (2) They affirm the utility of human virtual task models of rat spatial memory tasks; (3) They support one interpretation of the dampening of the hippocampal functional MRI (fMRI) blood oxygen level-dependent (BOLD) signal during performance of the virtual radial arm maze observed by Astur et al. (2005).

Formation of Spatial Memory in Rats with Ischemic Lesions to the Prefrontal Cortex; Effects of a Synthetic Analog of ACTH(4-7)

Photochemically induced thrombosis of blood vessels in the prefrontal cortex in rats was shown to lead to ischemic infarcts in the lesion zone. Bilateral ischemic lesioning of the prefrontal cortex degraded measures of spatial memory when animals were tested in a Morris water maze with an invisible platform 20-24 days after surgery. Chronic intranasal administration of the peptide Met-Glu-His-Phe-Pro-Gly-Pro (Semax), a synthetic analog of ACTH(4-7), at a dose of 250 microg/kg/day during the first six days after photothrombosis, led to recovery of the animals' learning ability. The long-term antiamnestic action of the peptide observed here may result from its neuroprotective activity and its ability to stimulate the synthesis of neurotrophic factors.

Environmental and tactile stimulation modulates the neonatal handling effect on adult rat spatial memory

Handling of rat pups promotes their adult cognitive performance. However, new data suggest that individual components of the handling procedure, like exposure to novelty or tactile stimulation, have distinct lasting effects on behaviour. In this study we examined the interaction of early novelty exposure with a varying amount of tactile stimulation on spatial recognition memory and corticosterone secretion of adult male and female rats. A split litter design was used and the experimental animals were also compared to animal facility reared controls. The experiment was conducted in two phases. In the first phase, we examined the effect of novel or home environment during the 15-min of neonatal handling, following 10 back-strokes. Tactile stimulation of 10 back-strokes combined with novelty exposure, enhanced novel arm discrimination in a Y-maze task in adult rats of both sexes compared to their siblings that stayed at home, as well as to the animal facility reared controls. In the second phase, additional back-stroking (total of 20 back-strokes) reduced the Y-maze performance of males neonatally exposed to novelty, while the same treatment enhanced the performance of their siblings that stayed at home. Basal corticosterone levels, determined 1 week post-Y-maze, were significantly increased only in the novelty exposed/10 back-stroked females compared to same sex non-handled controls. In contrast, 10 back-strokes combined with the home cage environment increased corticosterone in males. Increase to 20 back-strokes reversed the impact of neonatal environment on corticosterone levels.These data suggest that the nature and intensity of the individual components of a mild early life manipulation, like handling, are critical in modifying aspects of adult memory performance and basal adrenocortical function.

Biphasic Effects of Forskolin on Tau Phosphorylation and Spatial Memory in Rats

To explore the role of protein kinase A (PKA) in regulating tau phosphorylation and spatial memory, we injected forskolin, an activator of PKA, at different concentrations into the rat brains. We found that forskolin at concentrations up to 80 microM enhanced tau phosphorylation and was associated with prominent spatial memory impairment. Higher concentrations of forskolin, up to 200 microM, were associated with reduced phosphorylation levels of tau and no memory deficits. Forskolin elevated cAMP and activated PKA in a dose-dependent manner. When infused at 200 microM, forskolin also resulted in the activation and overexpression of protein phosphatase-2A (PP-2A) and attenuated the okadaic acid-induced PP-2A inhibition. These data suggest that the upregulation of PKA by forskolin to a certain level may activate PP-2A but that the latter can ameliorate the PKA-induced tau phosphorylation and memory impairment in the rats.

Effect of different concentrations of forskolin on tau phosphorylation and spatial memory in rats and the underlying mechanism

Effect of different concentrations of forskolin on tau phosphorylation and spatial memory in rats and the underlying mechanism

T-817MA, a neurotrophic agent, ameliorates the deficits in adult neurogenesis and spatial memory in rats infused i.c.v. with amyloid-beta peptide.

Adult neurogenesis occurs throughout life in the subgranular zone and the dentate gyrus of the hippocampus. Deficient neurogenesis may be responsible for deficient hippocampal functions in neurodegenerative disorders such as Alzheimer's disease (AD). T-817MA [1-{3-[2-(1-Benzothiophen-5-yl)ethoxy] propyl}-3-azetidinol maleate] is a newly synthesized agent for AD treatment with neuroprotective effects against toxicity from amyloid-beta peptide (Abeta) and actions promoting neurite outgrowth in vitro. Furthermore, systemic administration of T-817MA ameliorated cognitive dysfunctions caused by neurodegeneration in a rat model of AD, induced by intracerebroventricular (i.c.v.) infusion of Abeta. The present study investigated quantitative relationships between spatial memory performance in Abeta-infused rats and hippocampal neurogenesis, and the effects of T-817MA on neuronal proliferation in vivo. Seven weeks after infusion of Abeta (peptide 1-40; 300 pmol.day(-1); i.c.v.), rats were tested in a place learning task in which they were required to alternately visit two reward places in an open field to obtain intracranial self-stimulation as rewards. Rats given Abeta infusions for 10 weeks displayed spatial memory impairments and a decrease in neurogenesis compared with those infused with vehicle. Treatment of the Abeta-infused rats with T-817MA (8.4 mg.kg(-1).day(-1), p.o.) significantly increased hippocampal neurogenesis and ameliorated spatial learning impairments. Furthermore, spatial learning in the task was significantly correlated with neurogenesis. These results suggest that defective hippocampal neurogenesis is a new target for AD treatment. The neurotrophic compound T-817MA increased hippocampal neurogenesis in an AD model and might be useful for treatment of AD patients.

Secreted amyloid precursor protein-α upregulates synaptic protein synthesis by a protein kinase G-dependent mechanism

Secreted amyloid precursor protein-α (sAPPα) is a neuroprotective and neurotrophic protein derived from the parent APP molecule. We have shown that sAPPα enhances long-term potentiation in vivo and can restore spatial memory in rats whose endogenous sAPPα production is impaired. These observations imply that the reduction of sAPPα levels seen in Alzheimer's disease, which occurs alongside increased levels of toxic amyloid-β, may be aetiologically significant. The mechanism by which sAPPα brings about changes in plasticity at synapses remains unresolved. We hypothesised that sAPPα may stimulate changes in synaptodendritic protein synthesis, an important mechanism for normal plasticity. To test this hypothesis, we investigated the effect of sAPPα on protein synthesis in synaptoneurosomes prepared from the hippocampi of adult male Sprague–Dawley rats. sAPPα (10 nM) significantly increased de novo protein synthesis as measured by the incorporation of [ 35S]-methionine into acid-insoluble proteins. This was dose-dependent and blocked completely by inhibitors of protein synthesis (cycloheximide) and of cGMP-dependent protein kinase (KT5823). Inhibitors of calcium/calmodulin-dependent protein kinases (KN62) and mitogen-activated protein kinase (PD98059) partially blocked the response. Further, the sAPPα-induced increase in protein synthesis was significantly attenuated when measured in synapses isolated from aged rats. These observations imply de novo protein synthesis at synapses may contribute to the long-lasting modulatory effects of sAPPα on synaptic plasticity.

Amyloid-β 25–35 impairs memory and increases NO in the temporal cortex of rats

β-Amyloid plays an important role in the neurodegeneration process of Alzheimer's disease (AD), but its neurotoxic mechanisms are not clear. It has been associated with the increase of oxidative stress and cognitive impairment because the β-amyloid peptide 25–35 (Aβ (25–35)) has the critical neurotoxic properties of the full-length Aβ 1–42. Our present study shows the role of Aβ (25–35) when injected into the temporal cortex on the nitric oxide pathways, 3-nitrotyrosine, neuronal death, and the spatial memory of rats 1 month after the injection. Our data showed that Aβ (25–35) increases oxidative stress, causes neuronal damage, and decreases spatial memory in rats. Notably, the injection of the fraction Aβ (25–35) caused an increase of nNOS and iNOS immunoreactivity in the temporal cortex and hippocampus. We demonstrated a significant increase of reactive astrocytosis, which was accompanied by neuronal damage in the temporal cortex and hippocampus of rats injected with Aβ (25–35). These data suggest that the fraction Aβ (25–35) injected into the temporal cortex might contribute to understanding the role of nitric oxide on the biological changes related to the neuropathological progression and the memory impairment in AD.

Differentiations of the effect of NMDA on the spatial learning of rats with 4 and 12 week diabetes mellitus.

This study examines possible interactions between behavioral effects and influence of N-methyl-D-aspartate acid (NMDA) receptors in 4 and 12-week streptozotocin (STZ) induced diabetic rats. Effects of NMDA receptor agonist on spatial learning were tested in control groups of rats and in rats with 4 and 12 weeks diabetes mellitus (DM). Experimental diabetes was induced by a single intravenous injection of streptozotocin at a dose of 65 m/kg, dissolved in citrate buffer. We used the water maze task and examined the acquisition and the retrieval of spatial memory in rats. In our present experiments, we observed that DM had no significant influence on acquisition and retrieval in 4 week diabetic rats on Morris water maze, but impaired examined parameters in 12 week diabetic rats in this test. The NMDA receptor agonist did not influence acquisition but increased recall on water maze in 12 week streptozotocin diabetic rats.

Cognitive Aging: A Common Decline of Episodic Recollection and Spatial Memory in Rats

In humans, recognition memory declines with aging, and this impairment is characterized by a selective loss in recollection of previously studied items contrasted with relative sparing of familiarity for items in the study list. Rodent models of cognitive aging have focused on water maze learning and have demonstrated an age-associated loss in spatial, but not cued memory. The current study examined odor recognition memory in young and aged rats and compared performance in recognition with that in water maze learning. In the recognition task, young rats used both recollection and familiarity. In contrast, the aged rats showed a selective loss of recollection and relative sparing of familiarity, similar to the effects of hippocampal damage. Furthermore, performance on the recall component, but not the familiarity component, of recognition was correlated with spatial memory and recollection was poorer in aged rats that were also impaired in spatial memory. These results extend the pattern of impairment in recollection and relative sparing of familiarity observed in human cognitive aging to rats, and suggest a common age-related impairment in both spatial learning and the recollective component of nonspatial recognition memory.

Spatial memory in rats after 25 hours

We investigated the time course of spatial-memory decay in rats using an eight-arm radial maze. It is well established that performance remains high with retention intervals as long as 4 h, but declines to chance with a 24-h retention interval (Beatty, W. W., & Shavalia, D. A. (1980b). Spatial memory in rats: time course of working memory and effect of anesthetics. Behavioral & Neural Biology, 28, 454–462). It is possible that 24 h reflects a genuine retention limitation of rat spatial memory. Alternatively, it may be possible to identify factors that might support memory performance even after very long delays. The current experiment was conducted to test the above two hypotheses. We evaluated performance using two intertrial intervals (24 and 48 h) and two retention intervals (1 and 25 h). Increasing the intertrial interval produced an approximately constant increase in performance for both retention intervals. This improvement is consistent with a trial-spacing effect (i.e., the superiority of spaced over massed trials). Rat spatial memory apparently lasts at least 25 h.

Morphofunctional state of neurons in the temporal cortex and hippocampus in relation to the level of spatial memory in rats after ablation of the olfactory bulbs

Ablation of the olfactory bulbs (bulbectomy) in mice and guinea pigs evokes a neurodegenerative process which, in terms of its morphological, biochemical, and behavioral features, is similar to Alzheimer's disease. We report here studies of the long-term sequelae of bulbectomy in rats. One year after surgery, testing of spatial memory in bulbectomized rats (BER) allowed the animals to be divided into two groups-those with good memory (BER-gm) and those with poor memory (BER-pm). Quantitative analysis of the morphofunctional state of neurons showed that BER-pm, as compared with the BER-gm group, had more marked pathological lesions in neurons of the temporal cortex and hippocampus, with significant increases in the numbers of cells showing pyknosis, karyolysis, cytolysis, and vacuolization. Both groups showed decreases in the distribution density of cells in the cortex. In terms of the level of brain beta-amyloid, the study groups fell in the order: BER-pm>BER-gm>control sham-operated rats. These results provide evidence of the long-term nature of changes in the morphofunctional state of neurons in the brains of BER, correlating with their levels of spatial memory.

Effects of acute systemic and intra-cerebral stimulation of cannabinoid receptors on sensorimotor gating, locomotion and spatial memory in rats

Cannabinoid CB(1) receptors in the brain are targets of both endocannabinoid signalling and the psychoactive compounds of the hemp plant. They mediate neuronal effects of their ligands in various corticolimbic and striatal circuits by presynaptic regulation of transmitter release. This study investigates acute systemic effects of the full CB(1) receptor agonist WIN 55,212-2 (WIN) on prepulse inhibition (PPI) of the acoustic startle response (ASR), locomotor activity and spatial memory retrieval in an eight-arm radial-maze task. Furthermore, we tested the effect of local intra-cerebral micro-infusions of WIN into the nucleus accumbens (NAc), ventral tegmental area (VTA), dorsal (dHIP) and ventral (vHIP) hippocampus and medial prefrontal cortex (mPFC). Systemic WIN (1.2 mg/kg) reduced PPI without affecting ASR, had no effect on locomotion in the open field, but impaired retrieval of spatial memory. Infusions of 5 microg/0.3 microl WIN into either NAc (core or shell), dHIP or VTA did not affect PPI and locomotion immediately afterwards. However, PPI was significantly reduced after intra-mPFC and intra-vHIP infusion of WIN. Furthermore, WIN infusion into dHIP increased the number of reference memory errors in the maze, suggesting impairment of memory retrieval. Our data support the notion that CB(1) receptor stimulation impairs sensorimotor gating most likely by modulation of neurotransmitter release in mPFC and vHIP. The lack of effects of local WIN infusions in NAc and VTA might be due to low receptor abundance in these regions. Additionally, CB(1) receptor activation in dHIP impairs spatial memory retrieval. Taken together, cortico-hippocampal cannabinoid receptors play an essential role in the regulation of cognitive and behavioural processes.

Different effects of chronic forced swim and restraint stress upon the rat spatial learning and memory

Objective To observe the effect of chronic forced swim or restraint stress on the rat's spatial learning and memory performance.Methods Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups:control group(rats receiving neither stress);chronic forced swim stress (FST) group(rats were forced to swim daily for 20 minutes during 14 days);and chronic restraint stress (CRS) group(rats were loosely restrained daily in a transparent plastic cylinder which made the rats could not move freely for 6 hours during 14 days).1,2 or 3 weeks after the final secession of either stress,the navigation test and probe test of Morris water maze were employed to evaluate the rat's spatial learning and memory ability,respectively.Results (1) 1 and 2 weeks after the final stress secession,the averaged escape latency of FST group in the navigation test was significantly shortened [1week:FST (14.56±2.17)s,(17.93±2.08)s,CONTROL(26.12±5.04)s,(25.22±2.80)s,t=11.21 and 7.25,P＜0.05];meanwhile,the averaged ratio of time spent in the target quadrant for the FST group in the probe test was significantly higher than that of the control group(P＜0.05).3 weeks after the final stress secession,there was no significant difference in the escape latencies and the ratio of time spent in the target quadrant between control and FST group.(2) 1 week after the final stress secession,both the averaged escape latency in the navigation test and the averaged ratio of time spent in the target quadrant for the probe test of CRS group were significantly changed when compared with that of the control group (P＜0.05).While 2 or 3 weeks after the final stress secession,these differences disappeared.Conclusion Chronic forced swim enhanced while the chronic low intensity restrain impaired rat's spatial learning and memory.These effects could not last long since the difference disappeared as the rats withdrew from the stress for a relatively long period.Different patterns of chronic stress gave rise to different reversible influences upon the rat's spatial learning and memory. Key words: Stress ; Forced swim ; Chronic restraint ; Navigation test ; Probe test ;

Environmental cue saliency influences the vividness of a remote spatial memory in rats

The Morris water maze is frequently used to evaluate the acquisition and retrieval of spatial memories. Few experiments, however, have investigated the effects of environmental cue saliency on the strength or persistence of such memories after a short vs. long post-acquisition interval. Using a Morris water maze, we therefore tested in rats the effect of the saliency of distal cues on the vividness of a recent (5 days) vs. remote (25 days) memory. Rats trained in a cue-enriched vs. a cue-impoverished context showed a better overall level of performance during acquisition. Furthermore, the probe trials revealed that the rats trained and tested in the cue-impoverished context (1) spent less time in the target quadrant at the 25-day delay, and (2) swam shorter distances in the target area, with fewer crossings at both 5- and 25-day delays, as compared to their counterparts trained and tested in the cue-enriched context. Thus, the memory trace formed in the cue-enriched context shows better resistance to time, suggesting an implication of cue saliency in the vividness of a spatial memory.

Sub-chronical exposure to diphenyl diselenide enhances acquisition and retention of spatial memory in rats

The present study was conducted to evaluate the effects of exposure to diphenyl diselenide [(PhSe) 2] on cognitive performance and glutamatergic parameters in normal Wistar rats. Animals were subcutaneously exposed to (PhSe) 2 acutely (G1) and sub-chronically for 4 weeks (G20) at the dose of 5.0 mg/kg or 8 weeks (G40) at the dose of 2.5 mg/kg and evaluated for behavioral and neurochemical analyses. In the water-maze, a significant increase in the number of crossing in the platform local was observed in the probe trial for both groups exposed to (PhSe) 2 (G20 and G40). In the T-maze, the latency to reach the extremity of the arm in the trial 2 was lower in both groups exposed to (PhSe) 2 (G20 or G40) when compared to the respective control groups. In the open-field test, no significant differences in the number of crossing and rearing were observed among groups. Furthermore, the basal [ 3H]glutamate release by synaptosomes from whole brain of rats was significantly decreased in the G40 when compared to the control group. These findings suggest that sub-chronic exposure to (PhSe) 2 improved the performance of Wistar rats in the water-maze, a test that evaluates cognitive functions.

Hippocampal damage impairs long-term spatial memory in rats: Comparison between electrolytic and neurotoxic lesions

In previous studies we have suggested that the dorsal hippocampus is involved in spatial consolidation by showing that rats with electrolytic hippocampal lesions exhibit a profound deficit in the retention of an allocentric task 24 days after the acquisition. However, in various hippocampal-dependent tasks, several studies have shown an overestimation of the behavioral deficit when electrolytic versus axon-sparing cytotoxic lesions has been used. For this reason, in this report we compare the effects on spatial retention of electrolytic and neurotoxic lesions to the dorsal hippocampus. Results showed a similar deficit in spatial retention in both groups 24 days after acquisition. Thus, the hippocampus proper and not fibers of passage or extrahippocampal damage is directly responsible for the deficit in spatial retention seen in rats with electrolytic lesions.

Effect of head-only sub-chronic and chronic exposure to 900-MHz GSM electromagnetic fields on spatial memory in rats

Primary objective: This study was carried out to investigate the behavioural effects of sub-chronic and chronic head-only exposure to 900 MHz GSM (Global System for Mobile communications) in male rats.Methods: Rats were exposed for 45 minutes per day, at a brain-averaged specific absorption rate (SAR) = 1.5 W Kg−1or 15 minutes per day at a SAR = 6 W Kg−1, during 8 or 24 weeks. Then, their spatial memory was tested using the radial-arm maze. In the first phase (10 days), rats were trained to visit the eight arms of the maze without returning to an arm already visited. In the second phase (8 days), a 45-minute intra-trial delay was introduced after four visited arms.Results: Performance of exposed rats (1.5 or 6 W Kg−1) was compared with that of sham, negative control and positive control rats. Scopolamine treatment in the positive control rats induced deficit in spatial memory task in the second phase of the test. However, spatial memory task was unaffected in exposed rats.Conclusion: Sub-chronic and chronic head-only exposure of rats to GSM 900 MHz signal (45-minutes, SAR = 1.5 or 15-minutes, SAR = 6 W Kg−1) did not induce spatial memory deficit in the radial-arm maze.