Glucose facilitation of cognitive performance in healthy young adults: examination of the influence of fast-duration, time of day and pre-consumption plasma glucose levels

RATIONALE: Previous investigations have demonstrated increased performance after the administration of a glucose-load on certain aspects of cognitive functioning in healthy young adults. Generally these studies have used a procedure where participants were tested in the morning after an overnight fast. OBJECTIVE: The aim of the present study was, for the first time, to investigate the glucose cognitive facilitation effect under more natural testing times and with shorter duration of the previous fast. METHODS: Measures of verbal and non-verbal memory performance were compared under different fasting intervals (2-h fast versus overnight fast), times (morning versus afternoon) and glycaemic conditions (glucose versus aspartame drinks) in healthy young participants. RESULTS: There was a significant glucose facilitation effect on long-term verbal memory performance. In addition, glucose significantly enhanced long-term spatial memory performance. The effect of glucose was essentially equivalent whether it was given after an overnight fast or a 2-h fast following breakfast or lunch. There was no effect of drink and time of day on working memory performance. CONCLUSIONS: The results of this study further support the hypothesis that glucose administration can enhance certain aspects of memory performance in healthy young adults. More significantly, the findings indicate that this cognitive facilitation effect persists under more naturalistic conditions of glucose administration and is not restricted to long fast durations or morning administration.     

Glucose and memory: fractionation of enhancement effects?

Recent research findings indicate that glucose administration enhances some aspects of cognitive functioning. To date, those studies which have investigated the effects of glucose on memory in human participants have concentrated on its apparent ability to attenuate memory impairment. Relatively little research has been done in humans investigating the effects of glucose on memory performance in young healthy participants in whom no memory deficits exist. Moreover, the work which has been conducted in this population has produced somewhat equivocal findings. In this study, after overnight fasting the influence of a 25 g oral dosage of glucose on a range of measures of memory performance was investigated in healthy young female participants. Two control treatments (saccharin and water) were also administered. There was a significant glucose facilitation effect upon performance of long-term verbal free and cued recall tasks which did not vary with test delay. Performance on these free and cued verbal recall measures correlated significantly with blood glucose levels across all participants. No glucose-related facilitation was observed on either a test of short-term verbal memory (forwards/backwards digit recall) or a test of long-term non-verbal memory (complex figure reproduction). However, the significant glucose-related effects observed with long-term free and cued recall remained after controlling for participants’ differential baseline blood glucose levels and individual levels of immediate memory performance. Therefore, memory improvement after glucose ingestion was not merely a consequence of lower baseline blood glucose or lower immediate memory performance in the glucose treatment group. These findings indicate that there may be some fractionation in the memory facilitation effects of glucose: the memory enhancing effect of glucose administration in healthy young adults may be greatest on tests of long-term verbal recall. The results suggest that glucose may enhance retention in and/or retrieval from long-term verbal memory. Received: 11 July 1997/Final version: 27 October 1997     

An investigation into the effects of nicotine gum on short-term memory

Using a between-subjects 2 × 2 × 2 factorial design, 60 smokers and 60 non-smokers (equal number of males and females) performed a short-term memory task requiring delayed free recall of a visually presented supraspan word list. Using a double-blind procedure, half the subjects chewed nicotine gum and the other half chewed placebo gum prior to performing the memory task. Results support previous research findings which show that nicotine significantly improves short-term memory. Sex differences were also investigated, but findings showed no significant differences between male and female subjects. Methodological considerations are discussed and directions for future research are suggested. Received: 12 November 1997/Final version: 13 May 1998     

Effects of puromycin on memory for shuttle box extinction in goldfish and barpress extinction in rats

Five experiments were conducted to investigated the generality of puromycin's reported effect on disruption on memory of a recently learned task. The first experiment replicated previous work on acquisition to determine the effectiveness of the procedures used. The second investigated the role of puromycin's low pH in memory disruption. The third experiment used short training and extinction sessions to determine if puromycin retarded retention of extinction. The fourth experiment used longer training and extinction sessions and multiple and delayed injections of puromycin, and the fifth experiment attempted to extend puromycin's effect on avoidance extinction to extinction produced in an appetitive operant task. Puromycin disrupted retention of extinction of both shuttle box avoidance in fish and barpressing in rats. The role of puromycin's pH was negligible.     

Effects of smoking/nicotine on performance and event-related potentials during a short-term memory scanning task

RATIONALE: Nicotine absorbed from cigarette smoke shortens reaction time (RT) in a wide variety of cognitive tasks. However, relatively few studies have tried to isolate the specific stage(s) of information processing affected by smoking/nicotine. OBJECTIVE: The present study was designed to investigate the effect of smoking/nicotine on the short-term memory (STM) scanning stage of information processing in minimally abstaining smokers. Both RT and event-related potentials (ERPs) were measured. METHODS: A Sternberg-type STM-scanning task was performed before and after smoking each of two cigarettes. One cigarette had a 0.05-mg nicotine yield ("denicotinized") and the other had a 1.1-mg yield ("nicotine-yielding"). On each trial, either 2, 3, or 4 consonants were displayed as a memory set. After a brief interval, a single probe consonant was displayed. If the probe was in the memory set (positive probe) a right button press was required, and if the probe was not in the memory set (negative probe) the left button was pressed. RESULTS: Smoking the nicotine-yielding cigarette but not the denicotinized cigarette shortened RT. However, memory-scanning speed, as estimated from the increase in RT as a function of increasing set size, was not differentially affected by the two types of cigarettes. For the ERPs, smoking the nicotine-yielding but not the denicotinized cigarette (a) reduced N200 latency to both the memory-set stimuli and negative probes, (b) increased N200 amplitude to negative probes and P300 amplitude to both types of probes, and (c) produced a sustained negative shift in memory-set ERP amplitude beginning around 600 ms post-stimulus. CONCLUSION: While smoking/nicotine shortened probe RT, it did not affect the speed of STM scanning. Moreover, the ERP-latency effects obtained for the probes were small relative to the effects of smoking/nicotine on RT, suggesting that smoking/nicotine shortens RT primarily by affecting response-related processes.     

The effect of d-amphetamine on short-term memory for time in pigeons

The effect of d-amphetamine on pigeons' perception and short-term memory of time was investigated within a delayed symbolic matching to sample paradigm in which pigeons were rewarded for choosing one color after a 1-sec sample and another color after a 5-sec sample. On trials with no delay between sample offset and onset of the choice phase, d-amphetamine produced a bias toward choosing the color that was correct after long samples, suggesting that the birds overestimated the sample durations under amphetamine. With a 20-sec retention delay, d-amphetamine lowered choice accuracy to chance level, suggesting that it impaired the bird's short-term memory for sample durations. It was postulated that an amphetamine-induced increase in the rate of perceptual processing could mediate the effects of amphetamine on both time perception and memory.     

Differential effects of para-chlorophenylalanine on self-stimulation in caudate-putamen and lateral hypothalamus

Physostigmine was given intravenously to a total dose of 3 mg to 13 subjects; a placebo of 0.25 N saline was given intravenously to 10 other subjects; both groups received 1 mg of methscopolamine bromide subcutaneously preceding the intravenous infusions. A physostigmine syndrome consisting of decreased speech, slowed thoughts, mild sedation, expressionless faces, nausea, and decreased spontaneous activity was evident following doses of 1.5 to 2.0 mg of physostigmine. The capacity of short-term memory (STM) as measured by digit span tasks was significantly less for the subjects who received physostigmine than for the subjects who received placebo. No difference was observed between the two groups on tasks of consolidation from STM to long-term memory (LTM).Subiects who received physostigmine did not significantly differ from subjects who received placebo in their mood. However, two subjects in the physostigmine group, and no subjects in the saline group became tearful and depressed.     

Separate biochemical actions of inhibitors of short- and long-term memory

In vitro effects of the antibiotics - cycloheximide, puromycin and chloramphenicol, and the sodium pump blockers - ouabain, lithium and copper, on protein synthesis in the crude mitochondrial, postmitochondrial and synaptosomal fractions of chicken forebrain were studied. In the synaptosomal fraction there was a correlation between the inhibitions produced by the sodium pump blockers, of Na⁺/K⁺ ATPase activity, ¹⁴C-leucine uptake and the incorporation of ¹⁴C-leucine into protein; whereas the antibiotics only inhibited leucine incorporation into protein. The effects of these drugs on the in vivo incorporation of ¹⁴C-leucine into protein in various fractions of chicken forebrain were also studied. The results suggest that there is a biochemical link involving a sodium pump and the transport of amino acids, between nerve impulse activity and neuronal protein synthesis. This link may also interconvert short-term and long-term storage of memory.     

The effects of nicotinic acid and xanthinol nicotinate on human memory in different categories of age

The treatment effect of nicotinic acid and xanthinol nicotinate on human memory was compared with placebo in 96 healthy subjects. Forty-three subjects were young (35–45 years), 30 subjects middle aged (55–65 years) and 23 subjects were old aged (75–85 years). Pre- and post-treatment scores were measured on a battery of memory tasks, covering sensory register, short-term memory and long-term memory. The treatment regime was 1 dragee t.i.d. for 8 weeks. The administration of xanthinol nicotinate (500 mg, containing 141.7 mg nicotinic acid), nicotinic acid (141.7 mg) and placebo (lactose) was double-blind. Pre-and post-treatment scores were analysed by means of a multivariate covariance technique, the pre-treatment score serving as covariate. Nicotinic acid treatment resulted in improvement of sensory register and short-term memory, while xanthinol nicotinate improved sensory register, short-term memory and long-term memory. In comparison with placebo, both active compounds yielded improvements of 10–40%, depending on type of task. Treatment effects of nicotinic acid were predominantly found in the young and middle-aged, whereas treatment effects of xanthinol nicotinate were predominantly found in the old. These results are interpreted by the supposed activity of nicotinic acid at the cell membrane, improving neuronal transmission, and of xanthinol nicotinate inside the cell, enhancing cell metabolism and oxygen supply in the brain.This study was supported by a grant from Beecham Farma B.V.     

Blockade of adenosine A1 receptors in the posterior cingulate cortex facilitates memory in rats

Male Wistar rats were bilaterally implanted with indwelling cannulae in the caudal region of the posterior cingulate cortex. After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock) and received, immediately after training, a 0.5-microl infusion of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA; 1, 50 or 100 nM) or of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1, 25 or 50 nM). Animals were tested twice, 1.5 h and, again, 24 h after training, in order to examine the effects of these agents on short- and long-term memory, respectively. Only 50-nM DPCPX was effective in altering memory, promoting a facilitation. These results suggest that adenosine A1 receptors in the posterior cingulate cortex inhibit memory consolidation in a way that their blockade facilitates memory for inhibitory avoidance in rats.     

Paradoxical sleep and memory: Long-term disruptive effects of anisomycin

The effects of the protein synthesis inhibitor Anisomycin (ANI) on Paradoxical Sleep (PS or REM sleep), slow wave sleep (SWS), and retention of one-trial inhibitory avoidance training was examined in mice in three separate experiments. In Experiment 1, mice injected with ANI 120 mg/kg and 210 mg/kg exhibited reductions in PS for 9 consecutive hours and ANI 40 mg/kg treated mice for 6 consecutive hours with no PS rebound in all three groups. ANI increased SWS commencing 3 hr postinjection, continuing for 9 consecutive hours and then returning to saline control levels. There were no significant differences between ANI-treated groups in the degree of SWS augmentation. In Experiment 2, Part A, ANI 120 mg/kg and 210 mg/kg but not ANI 40 mg/kg impaired retention measured 72 hr after training. In Experiment 2, Part B, ANI 120 mg/kg and 210 mg/kg induced amnesia from 3 to 9 hr post-training but ANI 40 mg/kg was effective only from 3 to 6 hr. In Experiment 3, the gradient of memory trace susceptibility to disruption by ECS was extended to 3 hr post-training in mice given immediate post-training injections of ANI 40 mg/kg. ANI 20 mg/kg and ANI 10 mg/kg alone or in combination with ECS was ineffective in extending the lability of the memory trace. The results of this study indicate that PS in the 3 hr period after aversively motivated training is not essential for memory processing. We suggest that memory stability and maintenance is dependent on PS occurring over a protracted time period.     

Fuels for memory: the role of oxygen and glucose in memory enhancement

Recent studies indicate that some aspects of memory can be enhanced by the administration of oxygen or glucose. Considering the dependency of glucose metabolism upon oxygen supply, the present study predicted that administering a combination of 100% oxygen with glucose would have greater memory-enhancing effects than when either substance was administered alone. In a placebo-controlled study, 104 healthy adults were given a glucose or placebo drink, and inhaled 100% oxygen or air for 1 min, before carrying out a number of everyday memory tasks designed to measure short-term and long-term memory. Results showed support for the enhancing effects of oxygen (but not for glucose) on delayed recall. These findings are discussed in relation to the possible cholinergic properties of oxygen and glucose and the implications for their clinical use. Received: 19 June 1997/Final version: 15 October 1997     

Effects of marihuana on reaction time and short-term memory in human volunteers

Twenty-seven adult male marihuana smokers volunteered to participate in a hospital research ward study for a 31-day period. Following five days of baseline acclimatization, subjects could purchase and smoke marihuana cigarettes on a free choice basis for a period of 21 consecutive days. The marihuana smoking period was followed by a concluding five-day baseline. Measurements of simple reaction time, choice reaction time and short-term memory were carried out during the entire study. Analysis of variance revealed no statistically significant differences between control and marihuana performance; however, a correlational analysis showed that individual subject performances on all three tasks were significantly correlated from test session to test session during control conditions but not during marihuana smoking conditions. Findings are discussed in relation to attentional and motivational factors associated with performance on the three tasks.     

An hypothesis on the role of glucose in the mechanism of action of cognitive enhancers

This review presents evidence that some cognition enhancing drugs produce their beneficial effects on learning and memory by increasing the availability of glucose for uptake and utilization into the brain. The hypothesis further suggests that many cognition enhancing drugs act through a peripheral mechanism rather than directly on the brain. The general hypothesis is supported by four independent and converging pieces of evidence: 1) Some cognition enhancing drugs may not cross the blood-brain barrier, but can still facilitate memory; 2) Some cognition enhancing drugs are effective only when injected peripherally, but not when injected directly into the brain; 3) Many cognition enhancing drugs are not effective after adrenalectomy; 4) Cognitive function is correlated with glucose regulation in aged animals and humans. These four lines of research have implications for the role of glucose in the action of specific cognitive enhancers.     

香莲外洗液对念珠菌葡萄糖消耗的影响分析

目的 观察香莲外洗液对念珠菌葡萄糖消耗的影响,探讨香莲外洗液对念珠菌生长的抑制情况.方法 应用微量肉汤稀释法测定不同药液浓度香莲外洗液和氟康唑对3种念珠菌标准菌株ATCC22019、ATCC6258和耐药SC5314的葡萄糖消耗,以确定香莲外洗液对念珠菌生长的抑制作用.结果 香莲外洗液在药浓度≥0.98mg/ml时能大大降低这3种菌株对葡萄糖的消耗,作用效能较为一致;氟康唑药浓度分别在4μg/ml、32μg/ml 时ATCC22019和ATCC6258对葡萄糖消耗明显降低,而氟康唑药浓度在128μg/ml时SC5314葡萄糖消耗不降低.结论 香莲外洗液在药浓度≥0.98 mg/ml时念珠菌的葡萄糖消耗大大降低,并对对氟康唑天然耐药的ATCC6258和耐药SC5314念珠菌生长都有良好的抑制作用,有助于对临床难治念珠菌病的治疗.     

Comparative effects of alpha-2 receptor agents and THA on the performance of adult and aged rats in the delayed non-matching to position task

The present study investigated the effects of dexmedetomidine (an alpha-2 adrenoceptor agonist), atipamezole (an alpha-2 adrenoceptor antagonist) and tacrine (an inhibitor of acetylcholinesterase) on the performance of adult and aged rats in a delayed non-matching to position task assessing spatial short-term memory. Most of the aged rats were impaired in the pretraining phases and in the acquisition of the non-delayed version of the task. After a substantial training period of the delayed version of the task, both adult and aged rats reached their asymptotic level of performance. Both adult and aged rats showed a decline in the percent correct responses at the longest delays in this task, and a delay independent decrease in the percent correct responses across the delays (0–30 s) was found in the group of aged rats (25-month-old) as compared to the adults (10-month-old). Dexmedetomidine (0.3, 1.0 or 3.0 µg/kg), atipamezole (0.03, 0.3 or 3.0 mg/kg) and tacrine (1.0 or 3.0 mg/kg) did not increase the percent correct responses in adult or aged rats. The highest doses of dexmedetomidine and tacrine decreased behavioural activity of rats during this short-term memory testing. Atipamezole (0.03 mg/kg) increased behavioural activity of rats. The results suggest that acute, systemic administrations of alpha-2 drugs or an anticholinesterase do not improve short-term memory in rats.     

Effects of sodium barbitone on learning and memory-storage of an appetitive and an aversive task

In order to test the effects of sodium barbitone on the acquisition and retention of an appetitively and an aversively reinforced behavior, mice were trained in a spatial discrimination Y-maze task. Learning was observed in both situations, with acquisition unimpaired by the drug. Sodium barbitone did, however, affect retention of both tasks in all groups treated with the drug before training. Results are discussed in light of the various modes of action of this drug, i.e., as an inhibitor of protein synthesis, as a blocker of catecholamine biosynthesis, with regard to its effects on paradoxical sleep and on gamma-amino butyric acid (GABA).     

Effects of cigarette smoking and 12-h abstention on working memory during a serial-probe recognition task

Nicotine has been shown to affect attentional and mnemonic processes. However, whether these effects are due to changes in perceptual and/or motor aspects of the tasks is not at all clear. This study tested the hypothesis that nicotine from cigarette smoking has differential effects on perceptual and motor processes, as reflected by event-related potentials (ERPs) and reaction times (RTs), respectively, and that perceptual effects may be specific to changes in working memory. ERPs, RTs and performance accuracy were recorded from smokers and nonsmokers during a serial-probe recognition memory task in which lists of words or “memory sets” were followed by a probe word that was either in-set or out-of-set. Smokers were tested in a “smoking” and a 12-h “deprived” condition. Smoking-smokers and deprived-smokers exhibited fast RTs to in-set and out-of-set probes relative to a group of nonsmokers. They exhibited even faster RTs when the in-set probe word matched the first or last item in the memory set. Thus, smokers as a group showed enhanced primacy and recency effects suggesting that smoking specifically facilitates processes related to the motor output aspects of working memory. Different effects characterized the electrophysiology. Larger P300s were recorded to in-set compared to out-of-set probes by both subject groups. Smoking smokers exhibited enhanced P300s to both types of probes. When smokers abstained for 12 h (deprived smokers), the differences in P300 amplitude were reduced but not eliminated. Smoking smokers exhibited faster P300 latencies to in-set probes, while deprived smokers showed delayed latencies relative to nonsmokers. Primacy and recency P300 effects characterized nonsmokers and deprived smokers. However, this relationship was reversed in the Smoking condition. These results support the hypotheses that nicotine has distinct effects on memory-related perceptual and motor aspects of working memory. The increase in efficiency of the memory search with nicotine is consistent with the functional role of the cholinergic system in maintaining a state “appropriate for efficient information processing.” Received: 12 April 1997/Final version: 4 March 1998     

手术创伤对老年人血糖和理糖激素水平的影响

目的:探讨手术创伤对老年人糖代谢的影响。方法:测定青年和老年两组病人行胆囊切除术前后的血糖和血浆胰岛素、胰高血糖素及皮质醇等理糖激素水平。结果:术后5小时病人血糖升高,但老年组比青年组低20.4％,两组理糖激素水平无显著差异。术后21小时两组血糖持平,胰岛素升高,但老年组胰岛素水平比青年组低28.8％。结论:手术创伤后血糖代偿性升高,老年人的这种代偿能力下降,可能通过胰岛素升高幅度的减少进行代偿。     

鞘内注射罗哌卡因-葡萄糖液对大鼠脊髓蛋白质组的影响

目的研究鞘内注射混合了葡萄糖的罗哌卡因对大鼠行为学指标及脊髓蛋白质组的影响。方法 36只大鼠随机分为3组,经腰椎鞘内置管后,按组别给予0.5%罗哌卡因(R1组)、10%葡萄糖+等体积1%罗哌卡因配制成的0.5%罗哌卡因(R2组)及对照组(N组)。每次注入40μL,每间隔1.5 h 1次,共3次。首次注药前5 min及每次注药后10 min测一次血压;置管后1 h、末次注药后1 h及24 h,以BBB神经功能评分法及斜板试验记录运动恢复情况。最后一次评分结束后断头法处死大鼠,以导管尖端为中心切取5 mm脊髓组织提取蛋白并定量,采用双向凝胶电泳-飞行时间质谱技术鉴定差异蛋白质。结果 R2组在末次给药后收缩压较基础值明显下降(P<0.05),与同时点对照组比较差异有统计学意义(P<0.05);该组BBB评分及斜板实验结果较基础值也略有下降,但差异无统计学意义(P>0.05)。R1组无上述改变。与对照组相比,R2组中谷氨酰胺合成酶及醛糖还原酶的表达升高,NAD依赖的去乙酰化酶2表达下降。结论由葡萄糖稀释的0.5%罗哌卡因用于大鼠蛛网膜下腔,24 h后其脊髓蛋白质中与细胞能量代谢相关的酶ALDR及GS表达升高,与细胞增殖分化相关的SIRT-2表达下调。