Sandra E. File's research while affiliated with King's College London and other places

Publications (446)

Article
Full-text available
Acute doses of Ginkgo biloba have been shown to improve attention and memory in young, healthy participants, but there has been a lack of investigation into possible effects on executive function. In addition, only one study has investigated the effects of chronic treatment in young volunteers. This study was conducted to compare the effects of gin...
Article
There are relatively few studies of cognitive performance in the first few postmenopausal years and insufficient data on whether there is differential decline in different cognitive abilities. The aim of the present analysis was to determine the nature of cognitive decline across a range of functions within a period of 5 years from early to late po...
Article
After a brief outline of the nicotinic and cannabinoid systems, we review the interactions between the pharmacological effects of nicotine and cannabis, two of the most widely used drugs of dependence. These drugs are increasingly taken in combination, particularly among the adolescents and young adults. The review focuses on addiction-related proc...
Article
Fourteen patients (7 male, 7 female, 22-63 years), classified as having chronic fatigue syndrome (CFS), but without concurrent major depression, significant sleepiness or use of psychoactive medication, completed a double-blind, placebo-controlled, crossover study of the effects of the selective wakefulness-promoting agent, modafinil (200 and 400mg...
Article
The results of two previous studies on the effects of modafinil, a selective wakefulness-promoting agent, in healthy university students were combined in a retrospective analysis. This allowed determination of whether the effects of modafinil were dependent on IQ and whether the larger sample size (n=89) would reveal more cognitive benefits. A batt...
Article
Cannabinoid agonists induce complex and often contradictory effects on anxiety in humans and experimental animals. The data from animal tests provide evidence of dose-dependent bidirectional modulation of anxiety by the cannabinoid system and the importance of environmental context. The mechanisms mediating the effects of cannabinoids on anxiety-re...
Article
Four recent studies have investigated the effects of soya on cognition in post-menopausal women, with treatment periods ranging from 6 weeks to 12 months. This review assesses evidence as to whether there are any cognitive benefits from soya administration, and whether they are specific to particular cognitive processes. It also considers whether t...
Article
In a double-blind, parallel groups study, 60 healthy student volunteers (29 men and 31 women, aged 19-22 years) were randomly allocated to receive placebo, 100 or 200 mg modafinil. Two hours later, in the early evening, they completed an extensive cognitive battery. The 3 groups did not differ in self-ratings of sleepiness or tiredness before the t...
Article
To assess the effects of 6 weeks of treatment with soy supplements on mood, menopausal symptoms, and cognition in postmenopausal women not taking other forms of hormone therapy. In a double-blind, placebo-matched parallel groups study, 50 postmenopausal women (aged 51-66 y) were randomly allocated to receive daily treatment with a soy supplement (N...
Article
Gingko biloba has cognitive benefits both in populations suffering from dementia and after acute treatment in healthy volunteers, with some evidence indicating that those with poorer cognitive performance show greater benefit. We have previously found that 1 week of treatment with ginkgo improved attention, memory and mental flexibility in post-men...
Article
Animals trained to lick for a sucrose solution of a given incentive value that subsequently encounter an incentive downshift (i.e. 32-4% sucrose) display an exaggerated decrease in the amount consumed, relative to unshifted controls. This change has been classified as a successive negative contrast (SNC) effect. The emotional component to this robu...
Article
Self-ratings of mood and bodily symptoms were made by groups of IQ and education-matched male and female students [teetotal, low (2-9 units/week for both sexes; 1 UK unit=8 g alcohol) and moderate (12-34 units/week for males; 10-24 units/week for females) drinkers], before the start and at the end of cognitive testing. Multivariate analyses of vari...
Article
This study compared the mood and cognitive performance of male and female teetotal and binge drinking students. The binge drinkers had significantly lower self-ratings of trait anxiety and depression and of state alertness at the time of testing than did the teetotallers. The females had significantly higher ratings of trait and state anxiety, but...
Article
A survey was conducted in healthy volunteers to demonstrate the possible cognitive benefits of soy administration in diet. The student volunteers received 10 weeks of a low or high supervised soy diet. The post-menopausal women received placebo or a soy supplement for 12 weeks. Improved short-term memory for 12 or 6 weeks were also observed. The st...
Article
Men and women (50-67 years) completed drinking diaries and, on the basis of this, were divided into low (<2 units/day, 1 UK unit=8 g alcohol) and moderate (2-5 units/day) alcohol groups. They completed analogue rating scales of mood and bodily symptoms before and after two extended computerised cognitive tests. After the tests, the women showed sig...
Article
Animal tests of anxiety are used to screen novel compounds for anxiolytic or anxiogenic activity, to investigate the neurobiology of anxiety, and to assess the impact of other occurrences such as exposure to predator odors or early rearing experiences. This unit presents protocols for the most commonly used animal tests of anxiety. The Geller-Seift...
Article
Modafinil is a selective wakefulness-promoting agent that has been shown to enhance cognitive performance under conditions of sleep deprivation but which has equivocal effects in normal young volunteers. In a double-blind parallel group design study, 45 non-sleep-deprived middle-aged volunteers (20 men and 25 women, aged 50-67 years) were randomly...
Article
In spite of the addictive properties of cannabinoids, under certain circumstances, they can evoke strong anxiogenic and aversive responses in humans and in animal tests of anxiety. Effects of different doses of CP 55,940 (10, 20, and 40 microg/kg) were tested in the low-light, familiar (LF) apparatus test condition of the social interaction test. T...
Article
We have studied the possible interaction between the cannabinoid receptor agonist CP 55,940 (1 and 50 microg/kg) and the 5-HT1A receptor antagonist WAY 100635 (1 mg/kg) in the modulation of plus-maze and holeboard activity in Wistar adult male rats. In the plus-maze, the higher dose of CP 55,940 induced an anxiogenic-like effect, whereas the lower...
Article
Full-text available
Oestrogens affect fluid balance, influencing both ingestive behaviour and renal excretion. The renal effects are partly due to altered release of vasopressin and oxytocin. This study was designed to explore the role of oestrogen receptor-beta (ERbeta) in neurohypophysial hormonal function. Following dietary administration, soya isoflavones reach th...
Article
Oestrogens affect fluid balance, influencing both ingestive behaviour and renal excretion. The renal effects are partly due to altered release of vasopressin and oxytocin. This study was designed to explore the role of oestrogen receptor-beta (ERbeta) in neurohypophysial hormonal function. Following dietary administration, soya isoflavones reach th...
Article
As memory and concentration impairments are a frequent complaint in post-menopausal women, this well-defined population was selected to investigate the effect on mood and cognition of chronic treatment with Gincosan. In a double-blind placebo controlled study, post-menopausal women aged 51-66 were randomly assigned to 12 weeks' treatment with Ginco...
Article
Alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) and 5-hydroxytryptamine 1A (5-HT1A) receptors have been implicated in the anxiogenic effects of centrally administered nicotine, but the receptors that mediate the anxiogenic effects of systemic nicotine are not known. This study explored whether competitive nAChR antagonists [dihydro-beta-er...
Article
Full-text available
Anxiety may play a role in the initiation of smoking and there is evidence to suggest that sex and age may predetermine responses to nicotine. At present, the greatest increase in smoking is in women and it is often accompanied by dieting. The purpose of the present study was to investigate how the impact of dietary restriction might modify the eff...
Article
We previously reported that a high soya diet improved memory and frontal lobe function in young volunteers, and since soya isoflavones are agonists at oestrogen receptors, they may improve these functions in postmenopausal women. Thirty-three postmenopausal women (50-65 years) not receiving conventional hormone replacement therapy (HRT) were random...
Article
Clinical studies have suggested the involvement of 5-HT1A receptors in anxiety and depressive disorders because partial 5-HT1A receptor agonists such as buspirone are therapeutic. The present review considers evidence from genetic animal models that support a role for 5-HT1A receptors in anxiety-like and depressed-like behavior in animals. Selectiv...
Article
In a double-blind, placebo-controlled study, postmenopausal women (53-65 years old) were randomly assigned to 7-day treatment with Ginkgo (120 mg/day, n=15) or matched placebo (n=16). They were given a battery of cognitive tests and measurements of mood and menopausal symptoms at baseline (before treatment began) and at the end of 7 days. The group...
Article
Full-text available
Unconditioned anxiogenic effects of nicotine have been observed in the social interaction (SI) test 5 min after injection of a low dose and both 5 min and 30 min after injection of a high dose. Conditioned anxiety has also been observed 24 h after testing in the SI with a high dose of nicotine. In order to determine whether these three anxiogenic e...
Article
Most commercial rodent diets are formulated with soya protein and therefore contain soya isoflavones. Isoflavones form one of the main classes of phytoestrogens and have been found to exert both oestrogenic and anti-oestrogenic effects on the central nervous system. The effects have not been limited to reproductive behaviour, but include effects on...
Article
Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation. In a double-blind study we examined its effects in 30 healthy, non sleep-deprived students (19 men and 11 women, aged 19-23 years), who were randomly allocated to placebo, 100 or 200 mg modafinil and 3 h later completed 10...
Article
Nicotine has bimodal effects on anxiety, with low doses having an anxiolytic effect and high doses having an anxiogenic effect. The dorsal hippocampus is one of the brain areas that mediate the anxiogenic effect of nicotine through enhanced 5-HT release, but the nAChR subtype(s) that mediate these effects are not known. Intrahippocampal administrat...
Article
The effects of mild food deprivation (7 days of food restricted to once daily feeding to maintain body weights at 85% of free-feeding weights) were examined in adult male and female and adolescent female rats tested in the elevated plus maze and social interaction tests of anxiety. In adult male rats, food deprivation appeared to have an anxiolytic...
Article
Adult male hooded Lister rats were either fed a diet containing 150 microg/g soya phytoestrogens or a soya-free diet for 18 days. This concentration of phytoestrogens should have been sufficient to occupy the oestrogen-beta, but not the oestrogen-alpha, receptors. Using in situ hybridisation, significant reductions were found in brain-derived neuro...
Article
The social interaction test of anxiety was developed 25 years ago to provide an ethologically based test that was sensitive to both anxiolytic and anxiogenic effects. It is sensitive to a number of environmental and physiological factors that can affect anxiety. It has detected anxiogenic effects of peptides such as corticotropin-releasing factor (...
Article
Conditioning to the anxiogenic effects of nicotine has previously been demonstrated in the social interaction test and there was no generalization of conditioning between the social interaction and elevated plus-maze tests. Because the two tests generate distinct states of anxiety, the conditioning could have occurred to the cues associated with th...
Article
Full-text available
Despite its reinforcing properties nicotine has also been reported to produce anxiety in humans and anxiogenic effects in animal tests of anxiety. The aims of this study were three-fold: (a) to investigate whether anxiety can be conditioned to cues associated with an acute anxiogenic dose of nicotine, (b) to investigate whether the conditioned anxi...
Article
In a double-blind, placebo-controlled study, we examined the effects of nicotine (2 mg administered by inhalator) on the cognitive performance of male and female non-smoking students and on mood changes following a moderately stressful task. The groups were matched for age and IQ, and did not differ in pre-test measures of anxiety, depression, extr...
Article
In an open study, we determined whether there were sex differences in the mood ratings of non-deprived light smokers and nonsmokers under baseline conditions and after completing a battery of cognitive tests that were mildly stressful. Male and female students who were light smokers (5-12 cigarettes a day) were tested immediately after smoking thei...
Article
Oestrogen treatment has been found to improve memory in healthy post-menopausal women, but the effects are small, especially when socio-economic status is controlled. There is some evidence that with long-term treatment the benefits decline, or reverse. To examine the effects of 10 years of oestradiol implants on attention, memory and frontal lobe...
Article
This review focuses on nicotinic--serotonergic interactions in the central nervous system (CNS). Nicotine increases 5-hydroxytryptamine (5-HT) release in the cortex, striatum, hippocampus, dorsal raphé nucleus (DRN), hypothalamus, and spinal cord. As yet, there is little firm evidence for nicotinic receptors on serotonergic terminals and thus nicot...
Article
In an open study, self-ratings of bodily symptoms, mood (before and after stress), and cognitive performance were investigated in 25 women (aged 54-66 years) who for approximately 10 years had been taking an oral preparation of hormone replacement therapy (HRT), tibolone (Livial; 2.5 mg/ day). Tibolone has a unique profile, with estrogenic, progest...
Article
Rationale: Oestrogen treatment has been found to improve memory in healthy post-menopausal women, but the effects are small, especially when socio-economic status is controlled. There is some evidence that with long-term treatment the benefits decline, or reverse. Objective: To examine the effects of 10 years of oestradiol implants on attention, me...
Article
Nicotine has been reported to reduce anxiety in humans and in a number of animal tests. In the social interaction test of anxiety, administration of low doses of nicotine into the dorsal raphé nucleus (DRN) increases the time spent in social interaction without producing accompanying changes in locomotor activity, suggesting that nicotine acts spec...
Article
This review focuses on factors influencing behaviour in the elevated plus-maze, the holeboard and the social transmission of food preference. The elevated plus-maze provides independent measures of anxiety (percentage of time spent on open arms) and activity (number of closed arm entries) and can be used in both males and females. Important sex dif...
Article
In a double-blind, placebo-controlled study, we examined the effects of nicotine (2 mg administered by inhalator) on the cognitive performance of male and female non-smoking students and on mood changes following a moderately stressful task. The groups were matched for age and IQ, and did not differ in pre-test measures of anxiety, depression, extr...
Article
Soya foods are rich in isoflavone phytoestrogens with weak agonist activity at oestrogen receptors. Oestrogen treatment has been found to improve memory in men awaiting gender reassignment and in post-menopausal women. To examine the effects of supervised high versus low soya diets on attention, memory and frontal lobe function in young healthy adu...
Article
The gerbil social interaction test has previously detected anxiolytic effects of nicotine and diazepam. In the present study, the high affinity substance P (NK1) receptor antagonist L-760735 (3 mg/kg) significantly increased the time spent in social interaction, whereas its low affinity analogue L-781773 (3 mg/kg) was without effect. Diazepam (0.1...
Article
Anxiety may play an important role in the onset of smoking, particularly in young girls. This study examined whether there were sex differences in the effects of nicotine on anxiety in adolescent rats and whether social isolation modified these effects. Male and female adolescent rats were housed in groups of the same sex or in social isolation for...
Article
Rationale: Soya foods are rich in isoflavone phytoestrogens with weak agonist activity at oestrogen receptors. Oestrogen treatment has been found to improve memory in men awaiting gender reassignment and in post-menopausal women. Objective: To examine the effects of supervised high versus low soya diets on attention, memory and frontal lobe functio...
Article
Full-text available
Smokers frequently report that they obtain anxiety-reducing (anxiolytic) effects from smoking, and this may be one factor which contributes to nicotine dependence. The aim of this study was to investigate the role of the dorsal raphé nucleus (DRN) in mediating the acute anxiolytic effect of nicotine, the development of tolerance to this effect and...
Article
These experiments determined whether the housing conditions of rats influenced the effects of nicotine in two animal tests of anxiety, social interaction and elevated plus-maze tests. In animals housed singly for 7 days, (−)nicotine (0.025 mg kg−1 s.c.) was ineffective, but 0.05, 0.1 and 0.25 mg kg−1 (s.c.) significantly increased the time spent in...
Article
The effects of different treatment regimens were investigated on the development of tolerance to the anxiogenic effect of nicotine (0.45 mg/kg) in the social interaction test of anxiety. Rats received nicotine (0.45 mg/kg/day) by intravenous injections (5 days/week), subcutaneous injections (5 or 7 days/week) or continuous infusion by osmotic minip...
Article
In the social interaction test of anxiety, microinjections of midazolam (2-8 microg) into the dorsal hippocampus or dorsal raphé nucleus significantly increased the time spent in active social interaction, without changing locomotor activity, thus indicating specific anxiolytic effects. However, tolerance developed to these effects in rats that had...
Article
The purpose of this experiment was to compare, in three tasks of attention, the impairment caused by lorazepam (1 and 2.5 mg) administered to young volunteers with the impairment that results from aging. Performance on digit cancellation (DC), digit-symbol substitution (DSS), and Paced Auditory Serial Addition Task (PASAT) was significantly impaire...
Article
The purpose of the present experiment was to explore the role of the dorsal hippocampus in mediating the development of tolerance to the anxiogenic effect of nicotine in the social interaction test of anxiety, and to determine whether tolerance develops to the effects of nicotine on [3H]-5-HT release in this area. Nicotine (1 microg) administered b...
Article
The 5-HT(1A) receptor has previously been shown to be important in mediating the behavioural effects of nicotine. It is possible that nicotine administration might regulate the levels of 5-HT receptors in limbic and cortical regions, and such regulations may underlie adaptive responses to nicotine in the central nervous system. The effects of acute...
Article
In the elevated plus-maze test of anxiety, nicotine (0.1 mg/kg sc; 30 min after injection) had a significant anxiogenic effect, shown by specific decreases in the percentage of time spent on the open arms and in the percentage of open-arm entries. Tolerance developed to this anxiogenic effect after 7 days of nicotine treatment (0.1 mg/kg/day). Five...
Article
Most smokers report smoking has an anxiolytic effect, which may contribute to nicotine dependence. To examine effects in the social interaction test (SI) of anxiety after 4 weeks' self-administered nicotine (15 infusions of 0.03 mg/kg, totalling 0.45 mg/kg per day), and after 24 and 72 h of withdrawal. The effect of exposure to the operant chamber...
Article
The effects of two drugs with anxiolytic actions, diazepam (0.1, 0.3 and 1 mg/kg) and nicotine (0.1 and 0.5 mg/kg) were examined on the time spent in social interaction by pairs of male gerbils. In a test arena lit by high light, diazepam (0.1 mg/kg) increased social interaction, without changing locomotor activity. Diazepam (0.3 and 1 mg/kg) produ...
Article
Full-text available
Rationale: Smokers frequently report that they obtain anxiety-reducing (anxiolytic) effects from smoking, and this may be one factor which contributes to nicotine dependence. Objective: The aim of this study was to investigate the role of the dorsal raphé nucleus (DRN) in mediating the acute anxiolytic effect of nicotine, the development of toleran...
Article
Rationale: Most smokers report smoking has an anxiolytic effect, which may contribute to nicotine dependence. Objective: To examine effects in the social interaction test (SI) of anxiety after 4 weeks' self-administered nicotine (15 infusions of 0.03mg/kg, totalling 0.45mg/kg per day), and after 24 and 72h of withdrawal. The effect of exposure to t...
Article
Acute nicotine administration (0.5 mg/kg i.p.) significantly decreased BDNF mRNA levels in dentate gyrus, CA3 and CA1 subfields of the rat hippocampus 2 h and 24 h after administration. However, with 7 days nicotine treatment, tolerance developed to the inhibitory effect of nicotine on BDNF mRNA expression and there was a significant increase in BD...
Article
The effects of nicotine on 5-hydroxytryptamine (5-HT)release from serotonergic nerve endings in rat dorsal hippocampal slices werestudied. Nicotine (50-500 μM) caused a concentration-dependentincrease in 5-HT release. This effect was antagonised by mecamylamine (0.5μM), indicating an action at nicotinic receptors. Nicotine-evoked5-HT release was no...
Article
The purpose of the present study was to determine the role of the 5-HT1A receptors in the lateral septum in the mediation of the anxiogenic effects of nicotine in the social interaction and elevated plus maze tests of anxiety in the rat. Bilateral infusion of (-)-nicotine (4 and 8 microg) and of the 5-HT1A receptor agonist 8-OH-DPAT (200 and 500 ng...
Article
1.1. Different animal tests model different anxiety disorders. Thus, the social interaction test is a model of generalised anxiety disorder, plus-maze Trial 1 models elements of panic disorder and Trial 2 in the elevated plus-maze is a model of specific phobia.2.2. Studies of the neuroanatomical and neurochemical pathways controlling behaviour in t...
Article
Abstract The purpose of the present study was to determine the role of the 5-HT1A receptors in the lateral septum in the mediation of the anxiogenic effects of nicotine in the social interaction and elevated plus maze tests of anxiety in the rat. Bilateral infusion of (–)-nicotine (4 and 8 g) and of the 5-HT1A receptor agonist 8-OH-DPAT (200 and 5...
Article
Evidence is starting to accumulate that NK1 receptor antagonists might have anxiolytic effects in animal tests and in patients. To examine the effects of NKP608, a substance P antagonist acting at NK1 receptors, in various conditions of the social interaction test of anxiety and to determine its effects after 3 and 6 weeks of treatment. Rats were t...
Article
The amnesic properties of benzodiazepines result from an impairment in explicit (conscious) acquisition of new material. Explicit encoding of new material has consistently resulted in an increase in regional cerebral blood flow (rCBF) in the left prefrontal cortex, as measured by positron emission tomography (PET). PET was used to determine whether...
Article
A review of the literature suggests that the dorsal hippocampal serotonergic system, and, in particular, the postsynaptic 5-HT1A receptor, mediates an anxiogenic response, whereas endogenous dorsal hippocampal cholinergic tone mediates an anxiolytic response. Accordingly, it has been shown that direct dorsal hippocampal administration of the 5-HT1A...
Article