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PubMed1997

Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release.

The exogenous administration of cytidine-5'-diphosphate (CDP)-choline has been used extensively as a brain activator in different neurological disorders that are associated with memory deficits. A total of 50 rats were utilized to (a) determine whether exogenously administered CDP-choline could attenuate posttraumatic motor and spatial memory performance deficits and (b) determine whether intraperitoneal (i.p.) administration of CDP-choline increases acetylcholine (ACh) release in the dorsal hippocampus and neocortex. In the behavioral study, traumatic brain injury (TBI) was produced by lateral controlled cortical impact (2-mm deformation/6 m/sec) and administered CDP-choline (100 mg/kg) or saline daily for 18 days beginning 1 day postinjury. At 1 day postinjury, rats treated with CDP-choline 15 min prior to assessment performed significantly better than saline-treated rats. Between 14-18 days postinjury, CDP-choline-treated rats had significantly less cognitive (Morris water maze performance) deficits that injured saline-treated rats. CDP-choline treatment also attenuated the TBI-induced increased sensitivity to the memory-disrupting effects of scopolamine, a muscarinic antagonist. The microdialysis studies demonstrated for the first time that a single i.p. administration of CDP-choline can significantly increase extracellular levels of ACh in dorsal hippocampus and neocortex in normal, awake, freely moving rats. This article provides additional evidence that spatial memory performance deficits are, at least partially, associated with deficits in central cholinergic neurotransmission and that treatments that enhance ACh release in the chronic phase after TBI may attenuate cholinergic-dependent neurobehavioral deficits.

Acetylcholine↗
PubMed1990

Memory for Places and the Region of the Mamillary Bodies in Rats.

Rats with extensive lesions of the mamillary bodies and the immediately adjoining areas exhibited a severe impairment on two spatial memory tasks. In the first task, the animals had to retrieve food from each one of eight separate locations within the daily test session. In the second task, the animals were allowed to visit a particular location and retrieve food from it and, after a variable delay, they had to select between returning to the location they had already visited and a new location that now contained the food. Rats with lesions of the mamillary region were able to perform the task with minimal delay, but their performance was impaired as the delay increased. Finally, rats with mamillary lesions were not impaired in learning a visual discrimination task or its reversal. The results show that extensive damage in the mamillary region can lead to significant and long lasting spatial memory impairments.

Journal Article↗
PubMed2001

Stress, hippocampal plasticity, and spatial learning.

During the last two decades numerous studies have been conducted in an attempt to correlate the mechanisms of long-term potentiation (LTP) of hippocampal synaptic transmission with those required for spatial memory formation in the hippocampus. Because stressful events block the induction of hippocampal LTP, it has been suggested that deficits in spatial learning following stress may be related to suppression of LTP-like phenomena in the hippocampus. Here I review these studies and discuss them in light of the emerging view that stress may induce changes in thresholds for synaptic plasticity necessary for both LTP induction and spatial memory formation. This phenomenon, known as metaplasticity, may involve a glucocorticoid modulation of calcium homeostasis.

Animals↗
PubMed2007

Left ventricular mass, blood pressure, and lowered cognitive performance in the Framingham offspring.

The purpose of this study was to determine whether echocardiographic left ventricular mass is related to cognitive performance beyond casual blood pressure adjusting for the influence of other vascular risk factors. We used multivariable regression analyses to relate left ventricular mass assessed at a routine examination (1995-1998) to measures of cognitive ability obtained routinely (1998-2001) in 1673 Framingham Offspring Study participants (56% women; mean age: 57 years) free from stroke, transient ischemic attack, and dementia. We adjusted for the following covariates hierarchically: (1) age, education, sex, body weight, height, interval between left ventricular mass measurement and neuropsychological testing (basic model); (2) basic model+blood pressure+treatment for hypertension; and (3) basic model+blood pressure+treatment for hypertension+vascular risk factors and prevalent cardiovascular disease. For the basic model, left ventricular mass was inversely associated with abstract reasoning (similarities), visual-spatial memory and organization, and verbal memory. For the basic model+blood pressure+treatment for hypertension, left ventricular mass was inversely associated with similarities and visual-spatial memory and organization. For the basic+blood pressure+treatment for hypertension+risk factors+cardiovascular disease model, no significant associations were observed. Echocardiographic left ventricular mass is associated with cognitive performance beyond casual and time-averaged systolic blood pressure, but this association is attenuated and rendered nonsignificant with additional adjustment for cardiovascular risk factors and cardiovascular disease, thus suggesting that these variables play an important role in mediating the association between left ventricular mass and cognition.

Blood Pressure↗
PubMed2005

St John's wort (Hypericum perforatum) diminishes cognitive impairment caused by the chronic restraint stress in rats.

In this study we tested the hypothesis that St John's wort (Hypericum perforatum) may counteract stress-induced memory impairment. Object recognition test and Morris water maze were used to determine whether administration of H. perforatum (350 mg kg(-1) for 21 days), standardized to 0.3% hypericin content, protects against non-spatial and/or spatial memory impairments due to chronic restraint stress (2h daily for 21 days). A group of rats administered the exogenous corticosterone at the dose of 5 mg kg(-1) daily for 21 days, yielding its similar plasma levels as these observed in stress was run in parallel. In the first experiment all rats were tested for recognition memory in the object recognition test. On the following day, the animals were tested in open field and elevated "plus" maze to control for the contribution of respectively, motor and emotional effects of our treatments to the memory tests. In the second experiment, new group of stressed animals was tested for spatial memory in the water maze. We observed that H. perforatum prevented the deleterious effects of both chronic restraint stress and long-term corticosterone on learning and memory as measured in both, the object recognition and the water maze tests. The herb not only prevented stress- and corticosterone-induced memory impairments, but it significantly improved recognition memory (p<0.01) in comparison to control. These results suggest that H. perforatum has a potential to prevent stress memory disorders.

Animals↗
PubMed1983

Ablations of the mammillary nuclei in monkeys: effects on postoperative memory.

A new procedure was developed for ablating the mammillary nuclei in nonhuman primates via direct visual exposure. Using this technique, monkeys receiving lesions of the mammillary nuclei were compared to control animals after surgery to assess the retention of preoperatively acquired visuospatial discriminations and subsequent postoperative ability to attain a demanding spatial memory task. Although the lesions proved to be accurate and complete, no changes in gross behavior or deficits in preoperatively acquired visual and spatial behaviors were noted. The monkeys with mammillary body lesions were, however, impaired in their ability to acquire postoperatively the demanding spatial memory task. These findings are consistent with previous investigations suggesting that the mammillary bodies are involved in the acquisition of spatial discriminations and skills.

Animals↗
PubMed2005

Sex differences in a human analogue of the Radial Arm Maze: the "17-Box Maze Test".

This study investigated sex differences in spatial memory using a human analogue of the Radial Arm Maze: a revision on the Nine Box Maze originally developed by called the 17-Box Maze Test herein. The task encourages allocentric spatial processing, dissociates object from spatial memory, and incorporates a within-participants design to provide measures of location and object, working and reference memory. Healthy adult males and females (26 per group) were administered the 17-Box Maze Test, as well as mental rotation and a verbal IQ test. Females made significantly fewer errors on this task than males. However, post hoc analysis revealed that the significant sex difference was specific to object, rather than location, memory measures. These were medium to large effect sizes. The findings raise the issue of task- and component-specific sexual dimorphism in cognitive mapping.

Adolescent↗
PubMed2005

Effect of breakfast composition on cognitive processes in elementary school children.

The relationship between breakfast composition and cognitive performance was examined in elementary school children. Two experiments compared the effects of two common U.S. breakfast foods and no breakfast on children's cognition. Using a within-participant design, once a week for 3 weeks, children consumed one of two breakfasts or no breakfast and then completed a battery of cognitive tests. The two breakfasts were instant oatmeal and ready-to-eat cereal, which were similar in energy, but differed in macronutrient composition, processing characteristics, effects on digestion and metabolism, and glycemic score. Results with 9 to 11 year-olds replicated previous findings showing that breakfast intake enhances cognitive performance, particularly on tasks requiring processing of a complex visual display. The results extend previous findings by showing differential effects of breakfast type. Boys and girls showed enhanced spatial memory and girls showed improved short-term memory after consuming oatmeal. Results with 6 to 8 year-olds also showed effects of breakfast type. Younger children had better spatial memory and better auditory attention and girls exhibited better short-term memory after consuming oatmeal. Due to compositional differences in protein and fiber content, glycemic scores, and rate of digestion, oatmeal may provide a slower and more sustained energy source and consequently result in cognitive enhancement compared to low-fiber high glycemic ready-to-eat cereal. These results have important practical implications, suggesting the importance of what children consume for breakfast before school.

Attention↗
PubMed1993

Chronic nicotine ingestion improves radial arm maze performance in rats.

Effects of chronic nicotine treatment on spatial memory were studied in rats. After 3 weeks of administration of 2.5mg/kg/day in drinking water, the rats were submitted to a spatial learning task in an eight-arm radial maze, during which time the treatment was maintained. Chronic nicotine treatment improved daily spatial memory performance after the animals reached an asymptotic level. Nicotine-treated animals showed significantly better performance than control animals regarding the first error and the total correct path choices.

Journal Article↗
PubMed2003

Behavioral effects of arginine8-vasopressin in the Hebb-Williams maze.

Arginine(8)-vasopressin (AVP) has been shown to improve memory consolidation in various mnemonic tasks. Our previous studies have pointed out the involvement of the hippocampus (with higher sensitivity of its ventral part) in memory consolidation and retrieval processes during discriminative learning in mice. The present study was designed to extend our knowledge, firstly, of the range of tasks and consequently the types of information for which the peptide improves consolidation processes, and secondly, the effects of AVP on information treatment processes such an information transfer. To this end, the effects of AVP were analyzed in the Hebb-Williams closed-field maze. Mice were initially trained on one of the mazes in the Hebb-Williams series (Maze 7) and subsequently tested on either that maze or another maze in the series (Maze 11). The effects of the peptide on both memory consolidation and information transfer processes were analyzed in relation to the route of administration: peripheral (subcutaneous, s.c.), central (intracerebroventricular, i.c.v.), and in situ (dorsal or ventral hippocampus). The results showed that AVP facilitated spatial memory consolidation following s.c., i.c.v, and dorsal, but not ventral hippocampal administration. This differential effect of AVP following injection into the hippocampus can be interpreted in regards to this structure's functions. In line with the involvement of the dorsal hippocampus in spatial memory, the effectiveness of the peptide in the Hebb-Williams maze, which contains spatial components, was better when the treatment was performed in this part of the structure. In contrast, whatever the route of administration, AVP had no effect on processes related to the transfer from one learning situation to another.

Animals↗
PubMed2004

Effects of hippocampal lesions on acquisition and retention of spatial learning in zebra finches.

We tested the role of the hippocampus in spatial memory of zebra finches. The birds were trained to find the location of a food site among four identical feeders arranged on the aviary floor. Extra-maze cues were present. The birds had to perform the task from four different starting points. Successful visits and the time to find the food were recorded. Hippocampal lesions made before acquisition led to a decrease in correct choices. Hippocampal lesions following training disrupted the retention of the spatial memory. Surprisingly, birds with hippocampal damage reached the food as quickly as intact birds, but they needed more visits to find the correct feeder. Therefore, the birds with hippocampal damage used an alternative, nonspatial memory-based strategy to find the food.

Analysis of Variance↗
PubMed1997

Behavioral characterization of metrifonate-improved acquisition of spatial information in medial septum-lesioned rats.

We investigated the effects of acute oral pretraining treatment with an indirect acetylcholinesterase inhibitor, metrifonate, on water maze spatial navigation in medial septum-lesioned rats. We observed that metrifonate (30 mg/kg, orally) (1) does not alter the pattern of exploration of lesioned rats at the water maze pool or retrieval of spatial memory, (2) effectively reverses the acquisition defect, (3) enhances reversal learning, and (4) improves acquisition of water maze navigation by facilitating the encoding of the spatial representation of a specific environment. These results indicate that metrifonate does not improve escape performance to the hidden platform by modulating exploration strategy, but that metrifonate enhances the speed and accuracy of development and durability of spatial memory engrams, and facilitates learning capacity that depends on activity of the septo-hippocampal projection.

Acetylcholinesterase↗
PubMed2003

Age-related sex differences in spatial learning and basal forebrain cholinergic neurons in F344 rats.

Basal forebrain cholinergic neurons are important for spatial learning in rodents. Spatial learning ability is reportedly better in males than females, and declines with age. To examine the role of cholinergic function in sex- or age-related differences in spatial learning, we compared the size of basal forebrain cholinergic neurons (BFCN) of young and aged male and female Fischer 344 (F344) rats that had been trained in the Morris water maze. Young male and female rats were equally proficient in finding the platform during training trials, but probe tests revealed that young male rats had better knowledge of the platform's precise location. Impairments in spatial learning were observed in aged rats, and the advantage of males over females was lost. BFCN were significantly larger in young male than young female rats, and were correlated with spatial memory performance for both groups. BFCN were smaller in aged than young males; no change was seen between young and aged females. In the groups of aged rats the correlation between neuron size and spatial memory was lost. The present findings provide further evidence of a role for the basal forebrain cholinergic system in spatial learning, but reveal a complex interaction between sex, age and behavioral performance.

Aging↗
PubMed1988

Psychopharmacological effects in the radial-arm maze.

The radial-arm maze (RAM) has become a very widely used method for assessing spatial memory in rodents. It has proven to be quite useful in the investigation of the effects of a variety of pharmacological manipulations on spatial memory. The cholinergic system has been found to be crucial for accurate RAM performance. Blockade of either muscarinic or nicotinic receptors impairs performance. Other transmitter systems such as dopamine and the opiates have also been found to be involved with the maintenance of accurate RAM performance. This test has been found to be sensitive to the effects of a variety of toxicants given either in adulthood or during development. These findings provide a background for the assessment of the effects of novel substances on RAM performance as well as the basis for the further understanding of the neural substrates of memory.

Animals↗
PubMed2006

Spatial working memory deficits in adolescents at clinical high risk for schizophrenia.

Identifying endophenotypic markers is crucial to schizophrenia research for finding appropriate preventive strategies. Working memory (WM) deficit has been suggested as a marker for schizophrenia but its presence in adolescents at high risk is understudied. We piloted a test of spatial WM function in adolescents at clinical high risk (CHR) for schizophrenia and in age- and IQ-matched low-risk control subjects. CHR adolescents showed deficits in spatial WM compared with controls but showed intact performance on a non-WM-demanding spatial control task. Although based on a small pilot study, the results strongly suggest that WM deficit may be a risk factor for psychosis.

Adolescent↗
PubMed2003

N-methyl-D-aspartate prevented memory deficits induced by MK-801 in mice.

An interaction between N-methyl-D-aspartate (NMDA) and MK-801 was examined in mice using a modified elevated plus-maze paradigm that allows assessment of the adaptive form of spatial memory. NMDA administered (s.c.) immediately after the acquisition session protected the animals against the amnesia induced by MK-801 given shortly before the retention session. Behavioral performance, expressed as the transfer latency, and therefore spatial memory potency of NMDA plus MK-801 treated animals was comparable with that of both NMDA-treated animals and the controls.

Animals↗
PubMed1996

The effects of L-deprenyl on spatial short term memory in young and aged dogs.

1. Young and aged dogs were tested on a spatial memory task using a delayed non matching to sample technique. Dogs were tested with 20, 70 and 110 second delay intervals. Animals were pretrained to a stable level of performance prior to treatment. 2. During treatment periods, dogs were orally administered a placebo or I-deprenyl in doses of 0.5 and 1.0 mg/kg in a repeated measures design. 3. Young dogs did not show any significant effects of I-deprenyl, however the sample size was limited. 4. L-deprenyl administration improved spatial memory in aged dogs. 5. The optimal dose or length of treatment time of I-deprenyl varied among individual dogs.

Aging↗