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S E File

Publications and source records attributed to S E File.

At least 109 records · Page 6Linked to original sources
PubMed1993

Beware the builders: construction noise changes [14C]GABA release and uptake from amygdaloid and hippocampal slices in the rat.

The effects of exposure to chronic noise and vibration, produced by construction work, on the release and uptake of [3H]5-hydroxytryptamine ([3H]5-HT) and [14C]gamma-aminobutyric acid ([14C]GABA) from rat amygdaloid and hippocampal slices were investigated. Noise-exposure resulted in increased release, with no significant change in uptake, of [14C]GABA from amygdaloid slices. In hippocampal slices, [14C]GABA release was also increased, but the changes in release were dependent upon the marked decrease in uptake of [14C]GABA into these slices. There was an increase in peak K(+)-evoked release of [3H]5-HT from hippocampal slices, but no other changes in [3H]5-HT release or uptake in either region were observed following noise-exposure. These findings may have important practical implications for the research carried out in laboratories exposed to construction noise and vibrations.

Amygdala↗
PubMed1993

Social interaction and elevated plus-maze tests: changes in release and uptake of 5-HT and GABA.

Changes in release and uptake of [3H]5-HT and [14C]GABA were compared in slices taken from the hippocampus and frontal cortex of rats, left undisturbed in their home-cages, or exposed for 5 min to the elevated plus-maze or social interaction tests of anxiety. Exposure to the plus-maze decreased cortical GABA function (shown by decreased release) and increased hippocampal 5-HT function (shown by increased K(+)-evoked release but more markedly by decreased uptake). Compared with undisturbed home cage controls, only the high light, familiar condition of the social interaction test resulted in a significant increase in K(+)-evoked release of both [3H]5-HT and [14C]GABA from the hippocampus. All four social interaction test conditions resulted in increases in cortical uptake of [3H]5-HT and all but the high light, unfamiliar condition increased cortical uptake of [14C]GABA. Analysing the two factors manipulated in the social interaction test, unfamiliarity with the test arena resulted in increased uptake of hippocampal [3H]5-HT and decreased cortical [14C]GABA, whereas an increase in the level of light decreased the cortical uptake of [14C]GABA. The results show that changes in presynaptic function occur rapidly in response to a brief exposure to animal tests of anxiety. However, only the increased hippocampal release of 5-HT is likely to be causally linked to anxiety and the results show that this cannot be the sole explanation.

Animals↗
PubMed1993

Dissociation between behavioral and corticosterone responses on repeated exposures to cat odor.

Rats exposed for 5 min to a phobic stimulus (the odor of a cat) had plasma corticosterone concentrations significantly higher than those exposed to a neutral odor and than a group remaining undisturbed in the animal house. During the first exposure to cat odor the increased corticosterone was related to the avoidance behavior, measured as the time spent sheltering. After five exposures to cat odor the rats continued to avoid the odor cloth, but no longer responded with raised corticosterone levels. The results are discussed with reference to the two components of a phobic response (avoidance and disturbance), and it is suggested that the latter, reflected by changes in corticosterone, habituates more readily than the former.

Animal Communication↗
PubMed1993

Novel environment and cat odor change GABA and 5-HT release and uptake in the rat.

In hippocampal and cortical slices taken from rats moved in their home cages to a novel environment for 5 min, there were decreases in basal and K(+)-evoked [14C]GABA release and an increased [14C]GABA uptake compared with slices taken from rats remaining undisturbed in the animal house. The changes in 5-hydroxytryptamine (5-HT) release and uptake in response to a novel environment were markedly time dependent. In rats killed immediately after the 5-min exposure, there was decreased hippocampal [3H]5-HT uptake and higher hippocampal basal release, whereas in rats killed 30 min later there was increased [3H]5-HT uptake and lower basal release in both hippocampal and cortical slices. Rats exposed to cat odor in the novel environment showed increased release and decreased uptake of GABA in both brain areas compared with the group exposed to a neutral odor in the same novel environment, and these differences between the two odor groups were found both immediately and 30 min after the odor exposure. In contrast, only one measure of 5-HT function differed between the neutral and cat odor groups, with the latter showing increased cortical [3H]5-HT uptake 30 min after odor exposure.

Animals↗
PubMed1993

A comparison of rat brain amino acid and monoamine content in diazepam withdrawal and after exposure to a phobic stimulus.

1. The content of amino acids (taurine, glycine, glutamic acid, gamma-aminobutyric acid (GABA) and aspartic acid) and monoamines (5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline) in homogenates of rat cortical and hippocampal tissue were measured by high performance liquid chromatography (h.p.l.c.) with fluorescent and electrochemical detection respectively, after two anxiogenic treatments: exposure to a phobic stimulus (cat odour) and withdrawal from chronic diazepam treatment. 2. In neither of the two anxiogenic situations was there a significant change in any amino acid content, in either brain area. 3. In the group withdrawn from chronic diazepam, cortical 5-HT and 5-HIAA levels and hippocampal 5-HT levels were significantly increased. Noradrenaline content was significantly decreased in the hippocampus. 4. The changes in 5-HT and 5-HIAA levels following cat odour exposure were area-specific in that they decreased in the hippocampus, but increased in the cortex. 5. Following cat odour exposure, noradrenaline levels appeared not to change in either area studied. However during exposure to cat odour, it was found that half the animals avoided the odour source and half were indifferent. The animals showing marked avoidance had significantly higher cortical noradrenaline content and this was significantly different from control, whereas hippocampal noradrenaline levels were not dependent upon the differences in avoidance of the odour source. 6. The results show clearly different neurochemical changes in the rat following exposure to a phobic stimulus and withdrawal from diazepam. It is hoped comparative studies such as this will enable better understanding of anxiety states in the rat which could parallel the different classes of anxiety recognised in the clinic

Amino Acids↗
PubMed1993

The role of 5-HT in the anxiogenic effects of acute ethanol withdrawal and in the long-lasting cognitive deficits.

There was a significant increase in potassium-stimulated release of 3H-[5-HT] from hippocampal slices taken from rats withdrawn from chronic ethanol treatment, compared with control-treated rats. The anxiogenic behaviour observed 12 h after ethanol withdrawal was inhibited by the 5-HT1A partial agonist, buspirone (200 micrograms/kg s.c.), indicating that the increased 5-HT release might underlie the anxiogenic response. The ex-ethanol treated rats showed impaired habituation of motor activity in the holeboard and a reduced exploratory response. The latter, but not the former, were reversed by the 5-HT3 receptor antagonist, ondansetron (0.01 microgram/kg i.p.). Ondansetron was without effect on working memory errors, but significantly increased the number of reference memory errors made by the ex-ethanol group. It also had a significantly anxiogenic effect in this group. These results suggest that the chronic ethanol treatment changes the 5-HT system and has long-lasting effects on the function of 5-HT3 receptors.

Animals↗
PubMed1993

Benzodiazepine withdrawal: behavioural pharmacology and neurochemical changes.

This paper describes pharmacological treatments that can reverse the anxiogenic response detected in animal tests when rats are withdrawn from chronic treatment with diazepam. Concurrent treatment with the calcium channel antagonist verapamil prevented this withdrawal response and the benzodiazepine-receptor antagonist flumazenil reversed the anxiogenic response and restored the system to a drug-naive state. Other treatments that reversed the anxiogenic response were the GABAB agonist baclofen, the 5-HT1A receptor agonist buspirone, and the 5-HT3 receptor antagonist (R,S)-zacopride (GABA = gamma-aminobutyric acid; 5-HT = 5-hydroxytryptamine). Both the enantiomers of zacopride contributed to this reversal. These behavioural reversals are interpreted in the light of biochemical studies showing increased 45Ca2+ flux and [3H]5-HT release from the hippocampus, during benzodiazepine withdrawal (Fig. 1).

Animals↗
PubMed1993

Anxiogenic responses of rats on withdrawal from chronic ethanol treatment: effects of tianeptine.

Rats were fed a liquid diet with concentrations of ethanol increasing over 2 weeks and then maintained for 4 weeks to give a mean ethanol intake of 11.6 g/kg/day. They were withdrawn from ethanol for 12 hr and tested in two tests of anxiety, the social interaction and elevated plus-maze tests, and in the holeboard, which provides measures of exploration and motor activity. Compared with control animals that had received the liquid diet without ethanol, the rats withdrawn from ethanol showed significant reductions in social interaction, in the percentage of entries onto, and time spent on, the open arms of the plus-maze, and in measures of general activity in all three tests. Tianeptine, a tricyclic antidepressant which increases 5-HT uptake, reversed the anxiogenic responses and the hypoactivity detected in the social interaction test, but was without significant effect in the other tests.

Animals↗
PubMed1992

Modification of chlordiazepoxide's behavioural and neurochemical effects by handling and plus-maze experience.

The purpose of the present experiment was to determine how a rat's prior history (of repeated gentle handling and/or of the elevated plus-maze apparatus) modified the behavioural and neurochemical response to chlordiazepoxide. In handled animals one previous exposure to the plus-maze rendered the rats insensitive to the anxiolytic effects of chlordiazepoxide in this test. This phenomenon of 'one-trial tolerance' was not seen in unhandled rats and thus both prior handling and prior maze experience were necessary to abolish the behavioural response to chlordiazepoxide. The effects of chlordiazepoxide on K(+)-evoked [14C]GABA (gamma-aminobutyric acid) release were also modified by the rat's past history. The drug-induced reduction of GABA release in the cortex was abolished by prior plus-maze experience; whereas handling modified chlordiazepoxide's effects on GABA release in the hippocampus (the drug decreased release in unhandled rats and increased release in those given repeated gentle handling). Thus an anxiolytic response to chlordiazepoxide in the plus-maze was accompanied by reduced GABA release in both cortex and hippocampus. The 5-HT system (5-hydroxytryptamine) also proved sensitive to the rats' past history. The effects of chlordiazepoxide on K(+)-evoked [3H]5-HT release from the hippocampus depended on both prior handling and plus-maze experience and could be predicted from the undrugged level of evoked release; when this was low, chlordiazepoxide increased it, when it was high, chlordiazepoxide reduced it. These results raise the possibility that the beneficial effects of a benzodiazepine may depend on the baseline condition of the animals.

Animals↗
PubMed1992

The use of temazepam elixir in surgical dental sedation: a comparison with intravenous midazolam.

Out-patients attending for removal of at least one lower third molar were randomly allocated to treatment with temazepam elixir (n = 7) or intravenous midazolam (n = 8), as well as local analgesia. Patients were tested prior to drug administration and at the end of surgery. Both drugs increased heart rate and midazolam also decreased diastolic blood pressure. The two drugs caused significant, equal increases in ratings of sedation, but the reduction of anxiety was significant only for midazolam. There was significant amnesia for material presented after drug administration, as well as for dental events and this was significantly greater for midazolam. The effects of these drugs in dental patients were compared with those in normal volunteers treated in an identical manner, but without oral surgery. The drugs had similar significant cardiovascular and amnesic effects in the volunteers and the same effects on mood ratings, even though volunteers and patients differed in their pretreatment levels of anxiety and discontent. The dentist's ratings of the sedation and operating conditions were excellent in both cases. Thus temazepam elixir provided a useful sedative for oral surgery, avoiding the complications of intravenous administration. However, for equivalent levels of sedation, midazolam had greater anxiolytic and amnesic effects than temazepam.

Administration, Oral↗
PubMed1992

Acute handling stress downregulates benzodiazepine receptors: reversal by diazepam.

In rats naive to handling, the effects of an acute handling stress led to lower [3H]flunitrazepam binding in the frontal cortex, compared with animals previously habituated to handling for 2 or 21 days. This decreased binding was due to reductions in the number of receptors, not to change in affinity. Pre-incubation with diazepam (0.3, 3.0 or 30 microM) of frontal cortex homogenates taken from naive rats exposed to acute handling stress (followed by extensive washing to remove residual diazepam and endogenous modulators) led to a concentration-dependent increase in the number benzodiazepine receptors, without any change in KD. Acute in vivo administration of diazepam (4 mg/kg) prior to the handling stress was without significant effect in handling-habituated animals, but increased [3H]flunitrazepam binding in handling naive rats. Thus, handling habituation and diazepam treatment have similar actions on benzodiazepine binding and represent two ways of adapting to the stress of handling by increasing the number of benzodiazepine receptors.

Animals↗
PubMed1992

Are there changes in sensitivity to 5-HT3 receptor ligands following chronic diazepam treatment?

Administration of 1-(3-chlorophenyl)-biguanide (mCPB), a 5-HT3 receptor agonist (1 and 10 mg/kg IP), was found to be significantly anxiogenic in vehicle treated rats tested in the plus-maze, while having no significant effect in rats withdrawn for 24 h from 21 days diazepam treatment (2 mg/kg/day), suggesting a decreased agonist action at 5-HT3 receptors following withdrawal from chronic diazepam treatment. In the social interaction test, diazepam withdrawn rats showed a significant decrease in social interaction when compared to the chronic vehicle treated group. This anxiogenic response was reversed by low doses of zacopride (0.0001-0.01 mg/kg IP); in the vehicle treated animals 0.1 mg/kg was significantly anxiogenic. The overall pattern of results with zacopride is explained by suggesting that the anxiogenic effects of high doses of zacopride are detectable at low levels of 5-HT function and are due to an agonist action of the S-isomer in the rat at 5-HT3 receptors. The anxiolytic action of low doses is attributed to the R-isomer acting at the R-zacopride binding site and is enhanced in conditions of high 5-HT function, e.g. in the diazepam withdrawn rats. If this hypothesis is correct, then we would predict the R-isomer alone would be more effective in reversing the anxiogenic effects of diazepam withdrawal than the racemate, used here.

Animals↗
PubMed1992

Concurrent treatment with verapamil prevents diazepam withdrawal-induced anxiety, in the absence of altered calcium flux in cortical synaptosomes.

Rats, chronically treated with diazepam (4 mg/kg/day) for 28 days, displayed increased anxiety when tested in the elevated plus-maze, 42 hr after the last dose. This anxiogenic withdrawal response was entirely prevented by the concurrent administration of the calcium channel antagonist, verapamil. No anxiolytic effect of chronic administration of verapamil was observed in vehicle-treated rats. To investigate the possibility that increased calcium function in nerve terminals might underlie diazepam withdrawal-induced anxiety, the uptake by cortical synaptosomes of 45Ca2+ was studied. Both fast (3-sec) and slow (60-sec) phase uptake were measured. No changes in basal (5 mM), potassium-stimulated (55 mM) or net uptake were observed during either fast or slow phase uptake. It is concluded that increased calcium influx in nerve terminals in the cortex does not underlie the anxiogenic effect of withdrawal of the benzodiazepine but that further studies must be carried out in other regions of the brain.

Animals↗
PubMed1992

Effects of lorazepam on psychomotor performance: a comparison of independent-groups and repeated-measures designs.

The purpose of this study was to compare the sensitivity to the effects of lorazepam (2.5 mg) of a design using independent groups (random allocation of subjects to either a placebo or a lorazepam treatment) with a repeated-measures design (subjects tested both before and after lorazepam treatment). With both designs, it was possible to demonstrate significant and equal effects of lorazepam in tests based upon speed of responding: Lorazepam significantly increased simple reaction time and significantly decreased performance in number cancellation and symbol copying tasks. The independent-groups design was more sensitive (i.e., showed effects at a higher level of significance) to the lorazepam-induced impairment in episodic memory, as assessed in a picture recognition task, and to the lorazepam-induced impairment in a word completion task. Comparisons between the two control condition scores indicated that there were unlikely to be significant group differences with random allocation of a relative homogeneous group of volunteers, such as medical students. While either design would be appropriate for homogeneous populations, for a heterogeneous clinical population where groups cannot be matched the repeated-measures design would be preferable.

Adult↗
PubMed1992

Raised [3H]-5-HT release and 45Ca2+ uptake in diazepam withdrawal: inhibition by baclofen.

The effect of diazepam withdrawal (2 mg/kg/day) on release of [3H]-5-hydroxytryptamine(5-HT) and [14C]-GABA from rat cortical and hippocampal slices was studied. No changes in [14C]-GABA release (basal, K(+)-evoked, uptake) from slices of either region were observed. Similarly, all parameters of [3H]-5-HT release were unchanged in cortical slices. However, during diazepam withdrawal, depolarised [3H]-5-HT release from hippocampal slices was raised with no changes in basal release or uptake into the slices being found. This increase could be prevented by in vivo administration of 1 mg/kg baclofen--this dose having no significant effect on [3H]-5-HT release from hippocampal slices of control rats. To further investigate this effect, 45Ca2+ uptake into hippocampal synaptosomes was examined and found to be increased during withdrawal. This was blocked by in vitro addition of 10 microM (-)baclofen, which had no effect on 45Ca2+ uptake in controls. Inhibition of 45Ca2+ uptake by (-)baclofen was also enhanced in nonwithdrawn diazepam-treated rats, but not in rats treated acutely with diazepam. The results from both studies indicate that chronic diazepam treatment increases neuronal sensitivity to baclofen. These results are discussed with reference to the anxiogenic state during diazepam withdrawal and a recent report of reversal of this behaviour by baclofen.

Animals↗
PubMed1992

Chlordiazepoxide reduces the generalised anxiety, but not the direct responses, of rats exposed to cat odor.

Rats were treated for 5 days with vehicle or chlordiazepoxide (CDP, 5, 10, or 20 mg/kg/day) and then exposed to a cloth impregnated with a neutral or cat odor. Those exposed to cat odor made significantly fewer contacts with the cloth and spent less time in contact with it and more time sheltering than those exposed to the neutral odor. CDP (5 mg/kg) significantly increased the time in contact with both odor cloths, but there were no other significant effects in the cat odor group. Rats previously exposed to cat odor showed significant anxiogenic responses in the social interaction and elevated plus-maze tests that were significantly reversed by CDP. There was no reduction in the responses to the cat odor on a second occasion as a result of the first exposure occurring after treatment with CDP (5 or 20 mg/kg). The anxiogenic effects of pentylenetetrazole (20 mg/kg) as detected in the social interaction and plus-maze tests were unaffected by prior odor experience. It is suggested that during exposure to the cat odor the responses of rats reflect avoidance components of a phobic anxiety state. Benzodiazepines are relatively ineffective against these responses in contrast to their efficacy against the generalised anxiety responses detected in the social interaction and plus-maze tests.

Animals↗
PubMed1992

Effects of nitrendipine, chlordiazepoxide, flumazenil and baclofen on the increased anxiety resulting from alcohol withdrawal.

1. Male hooded Lister rats were fed a liquid diet containing 10% absolute ethanol for 4-5 weeks. Control rats received the liquid diet in amounts controlled to produce equal weight gain. 2. The rats were tested 7.5 h after withdrawal of ethanol and 30 min after i.p. injection with nitrendipine, chlordiazepoxide or baclofen or 20 min after i.p. injection with flumazenil. 3. Nitrendipine (25-100 mg/kg) was unable to reverse the anxiogenic responses detected on withdrawal from ethanol, but the highest dose did reduce withdrawal tremor. 4. Chlordiazepoxide (10 mg/kg), flumazenil (4 mg/kg) and baclofen (1.25 mg/kg) significantly reversed the anxiogenic response detected on withdrawal from ethanol. 5. These reversals of ethanol withdrawal responses are similar to the reversal of the increased anxiety detected on withdrawal from chronic treatment with benzodiazepines. 6. The mechanisms and clinical implications of these drug-induced reversals are discussed.

Animals↗