Biomedical subjects

Sandra E File

Publications and source records attributed to Sandra E File.

29 records · Page 2Linked to original sources

PubMed2003

Soya phytoestrogens change cortical and hippocampal expression of BDNF mRNA in male rats.

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 neurotrophic factor (BDNF) mRNA expression in the CA3 and CA4 region of the hippocampus and in the cerebral cortex in the rats fed the diet containing phytoestrogens, compared with those on the soya-free diet. No changes in glutamic acid decarboxylase-67 or glial fibrillary acidic protein mRNA were found. This suggests a role for oestrogen-beta receptors in regulating BDNF mRNA expression.

Animals↗

PubMed2003

Modafinil affects mood, but not cognitive function, in healthy young volunteers.

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 100 mm visual analogue scales relating to mood and bodily symptoms, before and after an extensive battery of cognitive tests (pen and paper and CANTAB). There were no significant differences between the three treatment groups on any of the cognitive tests used in this study. There was a significant post-treatment change in the factor measuring 'somatic anxiety' and in individual ratings of 'shaking', 'palpitations', 'dizziness', 'restlessness', 'muscular tension', 'physical tiredness' and 'irritability', which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups. Further changes in mood were revealed after the stress of cognitive testing, with the 100 mg group showing greater increases in the 'psychological anxiety' and the 'aggressive mood' factors (as measured from the Bond and Lader scales).

Adult↗

PubMed2003

Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones.

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 randomly allocated in a double-blind parallel study to receive a soya supplement (60 mg total isoflavone equivalents/day) or placebo for 12 weeks. They received a battery of cognitive tests and completed analogue rating scales of mood and sleepiness, and a menopausal symptoms questionnaire before the start of treatment and then after 12 weeks of treatment. Those receiving the isoflavone supplement showed significantly greater improvements in recall of pictures and in a sustained attention task. The groups did not differ in their ability to learn rules, but the isoflavone supplement group showed significantly greater improvements in learning rule reversals. They also showed significantly greater improvement in a planning task. There was no effect of treatment on menopausal symptoms, self-ratings of mood, bodily symptoms or sleepiness. Thus, significant cognitive improvements in postmenopausal women can be gained from 12 weeks of consumption of a supplement containing soya isoflavones that are independent of any changes in menopausal symptoms, mood or sleepiness.

Aged↗

PubMed2003

Effects on cognition and mood in postmenopausal women of 1-week treatment with Ginkgo biloba.

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 treated with Ginkgo was significantly better than the placebo group in a matching-to-sample test of nonverbal memory, but the groups did not differ in immediate or delayed paragraph recall or in delayed recall of pictures. In a test of frontal lobe function (rule shifting) and in the Paced Auditory Serial Addition Test (PASAT) (which measures sustained attention but also involves frontal lobe function), the group treated with Ginkgo performed significantly better than the placebo group. However, the groups did not differ in a test of planning. The treatments did not differ in their effects on the volunteers' ratings of menopausal symptoms, sleepiness, bodily symptoms or aggression. The benefits of Ginkgo on memory and frontal lobe function found in this study are modest but are unlikely to be secondary to major mood changes.

Affect↗

PubMed2003

Involvement of 5-HT1A receptors in animal tests of anxiety and depression: evidence from genetic models.

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. Selective breeding for differential hypothermic responses to a selective 5-HT1A receptor agonist led to the development of the high DPAT sensitive (HDS) and low DPAT sensitive (LDS) lines of rats. The HDS rats differ from the LDS rats on several behavioral measures reflective of anxiety or depression, including reduced social interaction, reduced responding in a conflict task and exaggerated immobility in the forced swim test. However, they do not differ from the LDS rats in the elevated plus maze task, which is a commonly used test of anxiety. Nor do the HDS rats exhibit a typical anxiogenic response to the hippocampal administration of the 5-HT1A agonist. Although the HDS rats do exhibit elevations in 5-HT1A receptors in regions of the limbic cortex, it is not clear whether these increases account for the behavioral differences. Paradoxically, 5-HT1A receptor knockout mice also exhibit anxiety-like behavior in the plus maze, open field and conflict tests compared to wild type mice. However, the knockouts exhibited less immobility in the forced swim test than wild type control mice. Recent studies using selective regional reinstatement of the receptor have implicated the postsynaptic 5-HT1A receptors in these changes in anxiety-like behavior. Thus, preliminary evidence from two different types of genetic animal models suggests that anxiety-like behavior can arise if the 5-HT1A receptor function is eliminated or overexpressed. Further study with additional tests of anxiety are needed to confirm this intriguing relationship.

Animals↗

PubMed2002

Conditioned anxiety to nicotine.

RATIONALE: Despite its reinforcing properties nicotine has also been reported to produce anxiety in humans and anxiogenic effects in animal tests of anxiety. OBJECTIVE: 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 anxiety is specific to a particular test of anxiety, and (c) to investigate whether nicotine pre-exposure influences the development of a conditioned anxiogenic effect. METHODS: An anxiogenic dose of nicotine was administered to rats either before or after experience with the social interaction (SI) test. The retention of a conditioned anxiogenic response was examined when the rats were re-tested undrugged in the SI test 24 h later. To test whether conditioned anxiety was test specific, rats that had been tested in the elevated plus-maze with an anxiogenic dose of nicotine were retested undrugged in the SI test 24 h later, and vice versa. We then examined the effects of 4 days or 4 weeks pre-exposure to nicotine on the development of a conditioned anxiogenic response in the SI test. RESULTS: Rats injected with nicotine (0.45 mg/kg s.c.) 5 min before the social interaction test spent significantly less time in SI, indicating an unconditioned anxiogenic effect than did vehicle-injected controls or rats injected with nicotine after the test. After 24 h when all groups were tested undrugged only those previously tested in SI after nicotine injection showed a significant conditioned anxiogenic effect. This conditioned anxiety was test specific. Rats injected with nicotine before the SI test did not show an anxiogenic response when tested 24 h later undrugged in the plus-maze, and vice versa. Furthermore, although 4 days exposure to nicotine (0.45 mg/kg s.c.) did not prevent the development of a conditioned anxiogenic response, 4 weeks self-administration of nicotine (total dose, 0.45 mg/kg i.v) in an operant chamber did not affect the acute anxiogenic response to nicotine in the SI test, but it did prevent the development of conditioned anxiety. CONCLUSIONS: The present findings suggest that anxiety can be conditioned following exposure to an anxiogenic dose of nicotine, and that this anxiety is specific to the contextual cues associated with the SI test.

Animals↗

PubMed2002

Trough oestradiol levels associated with cognitive impairment in post-menopausal women after 10 years of oestradiol implants.

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, memory and frontal lobe function in healthy women (aged 51-72 years) who had undergone a surgical menopause. METHODS: In an open study, patients were recruited from the Guy's Hospital menopause clinic and were tested just before receiving a new implant. Exclusion criteria included any form of psychoactive medication, IQ<90, English not the first language and anxiety or depression scores in the clinical range. All patients had been receiving HRT with an oestradiol implant for about 10 years. Each patient was pair-matched to a woman who had never received HRT. Eighteen pairs were matched for age, IQ, socio-economic status, years of secondary education, and occupation. They completed questionnaires, mood rating scales and a battery of cognitive tests. RESULTS: The patients with oestradiol implants had significantly greater psychological and somatic menopausal symptoms and significantly worse mental flexibility (rule reversal) and long-term episodic memory than did the control group who had never received HRT. Analysis of covariance showed that the difference in menopausal symptoms did not account for the cognitive differences. There were no differences in a test of sustained attention or in a category generation task or in self-ratings of mood after the stress of cognitive testing. CONCLUSIONS: Long-term treatment with oestradiol implants does not convey cognitive benefits and may lead to impaired function.

Affect↗

PubMed2002

Nicotinic--serotonergic interactions in brain and behaviour.

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 nicotine's effects on 5-HT may not necessarily be directly mediated, but there is strong evidence that the 5-HT tone plays a permissive role in nicotine's effects. The effects in the cortex, hippocampus, and DRN involve stimulation of 5-HT(1A) receptors, and in the striatum, 5-HT(3) receptors. The 5-HT(1A) receptors in the DRN play a role in mediating the anxiolytic effects of nicotine and the 5-HT(1A) receptors in the dorsal hippocampus and lateral septum mediate its anxiogenic effects. The increased startle and anxiety during nicotine withdrawal is mediated by 5-HT(1A) and 5-HT(3) receptors. The locomotor stimulant effect of acute nicotine is mediated by 5-HT(1A) receptors and 5-HT(2) receptors may play a role in the expression of a sensitised response after chronic nicotine treatment. Unfortunately, the role of 5-HT(1A) receptors in mediating nicotine seeking has not yet been investigated and would seem an important area for future research. There is also evidence for nicotinic--serotonergic interactions in the acquisition of the water maze, passive avoidance, and impulsivity in the five-choice serial reaction task.

Animals↗

PubMed2002

Mood differences between male and female light smokers and nonsmokers.

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 their usual cigarette, at a time that they normally smoked. They were compared with a group of male and female students who were nonsmokers and did not differ on age, IQ, personality measures, anxiety or depression. Compared with the nonsmokers, both male and female smokers felt overall significantly more discontented, troubled, tense, quarrelsome, furious, impatient, hostile, annoyed and disgusted and experienced greater dizziness. The performance of distracting cognitive tasks did not reveal anxiolytic effects of smoking, and after performance of these tasks, both smokers and nonsmokers became more discontented and anxious. In addition, after the cognitive testing, both male and female smokers showed greater increases than nonsmokers in feeling spiteful, rebellious, incompetent and in sweating, suggesting that they experienced greater mood changes in response to cognitive stress. There were no overall differences between the smokers and nonsmokers in the performance of divided or sustained attention tasks or in episodic memory. It is unlikely that either nicotine withdrawal or differences in cognitive performance could account for the greater anxiety, discontent and aggressive mood that was found in smokers.

Adult↗

PubMed2002

Cognitive effects of 10 years of hormone-replacement therapy with tibolone.

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, progestogenic, and androgenic actions. The control group of 25 women had never taken HRT. Each woman in this group was pair-matched to one in the tibolone group on age, years since menopause, IQ, years of secondary education, and occupation. The groups were matched on their anxiety and depression scores on the Hospital Anxiety and Depression rating scale. Exclusion criteria were scores on this scale in the clinical range and any current illness or recent use of psychoactive medication. The women who were taking tibolone felt significantly less clumsy and had less severe palpitations than the control group. After exposure to a mildly stressful test, the control group felt more anxious, but this change was not seen in the group receiving tibolone. The group taking tibolone had significantly better semantic memory (memory for facts), as assessed in a category generation task, but they did not differ in tests of episodic memory (memory for events). An unexpected finding was that the tibolone group performed significantly worse on a sustained attention task and a planning task, tasks that are associated with frontal lobe function. Our results suggest that the effects of HRT on cognition may be influenced by the type of HRT, the duration of treatment, the nature of the tests, and the brain region controlling the cognitive function.

Arousal↗

PubMedDate not supplied

Age-associated sex differences in response to food deprivation in two animal tests of anxiety.

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 effect in the plus-maze as it significantly increased the percentage of entries onto open arms and the percentage of time spent on the open arms, without changing the number of closed arm entries. There were no effects of food deprivation in adult females, although in adolescent females food deprivation significantly increased the percentage of open arm entries rats. Adolescent female rats have female brains, but do not have circulating gonadal hormones and thus these results suggest that circulating female gonadal hormones are able to suppress some of the effects of mild food deprivation in the plus-maze. In the social interaction test, there were no effects of food deprivation in any group on the time spent in social interaction. There were opposite effects on locomotor activity in the adult male and female rats, with deprivation increasing activity in males and decreasing it in females. There were no effects of food deprivation on locomotor activity in the adolescent females, suggesting that circulating gonadal hormones were responsible for the bidirectional effects in the adult rats. In both tests there were age-associated differences in the female rats, with the adolescent females being less anxious (higher percentage of open arm entries and increased social interaction) than the adults.

Aging↗