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S E File

Publications and source records attributed to S E File.

At least 199 records · Page 11Linked to original sources
PubMed1986

Behavioral consequences of antidepressant treatment in rodents.

This review discusses the effects of antidepressant drugs on behaviors that are changed during the clinical treatment of depression. We first consider whether there is a similar subjective state produced by antidepressant drugs that might be akin to the mood changes caused clinically by these drugs. We thus review the evidence that antidepressant drugs can produce a distinctive enough subjective state to serve as a discriminative stimulus, and then discuss the nature of the cue produced. Secondly, we discuss whether there is any evidence that antidepressants enhance the rewarding aspects of stimuli since this aspect of behavior is reported to change during the successful treatment of depression. In this section we review the effects on electrical brain stimulation, water and food intake, exploratory and social behaviors. Finally, because of the proposed role of stress in the aetiology of depression, we review the effects of antidepressants on the responses to acute and chronic stress.

Aggression↗
PubMed1986

Is tofisopam an atypical anxiolytic?

This review describes the behavioural and biochemical profile of tofisopam, a 3,4-benzodiazepine that differs considerably in its effects and mechanisms of action from classical 1,4-benzodiazepines. In man tofisopam appears to possess anxiolytic activity without appreciable sedative and muscle relaxant side effects; in animals, however, tofisopam totally lacks anxiolytic and anticonvulsant properties in tests sensitive to the effects of 1,4-benzodiazepines. Tofisopam also has mixed dopamine agonist and antagonist-like properties in several in vivo and in vitro tests in animals. The possible relevance of the latter effects to the unusual behavioural profile of tofisopam are discussed, and its effects compared with those of buspirone, a novel anxiolytic that has similar activity at benzodiazepine and dopamine systems. It is proposed that these two drugs may represent a novel class of compounds that reduce anxiety by increasing the ability of patients to cope with daily tasks, rather than classical anxiolytics, that reduce anxiety by tranquilization.

Animals↗
PubMed1986

Aversive and appetitive properties of anxiogenic and anxiolytic agents.

The place-conditioning paradigm was used to assess the appetitive or aversive nature of anxiolytic and anxiogenic drugs. Rats were given a pre-conditioning preference test in which the time that they spent on each side of a two-compartment chamber was measured; each side was visually distinct. On two days they were confined to one side immediately after drug injection, and on alternate days they were confined to the other side after vehicle injection. The rats were then given a postconditioning preference test. The change in preference was used as the measure of the reinforcing properties of the drugs. The anxiolytic drugs diazepam, lorazepam, alprazolam, adinazolam, U-43, 465 and tracazolate produced a clear preference for the drug-associated side, indicating the appetitive qualities of these drugs. Preference was less clear for the anxiolytics chlordiazepoxide and buspirone. This suggests that it is possible to dissociate the rewarding and anxiolytic properties of drugs. All the anxiogenic drugs tested (CGS 8216, picrotoxin and yohimbine) produced conditioned aversion.

Animals↗
PubMed1986

Effects of chlordiazepoxide on competition for a preferred food in the rat.

In rats with previous experience of chocolate this is a food that is rapidly taken and eaten for which rats will compete. Female rats preferred white and milk chocolate to dark chocolate, but male rats displayed no preferences among the different types, regardless of whether it was offered in a novel environment or in the home-cage. Chronic (5 days) administration of chlordiazepoxide (5 mg/kg) to dominant animals, as judged in a previous competition for chocolate, led to a fall in success, whether the animals had been previously housed together for 1, 2 or 6 months. There were no significant effects of chlordiazepoxide treatment on the behaviour of subordinate rats. The potential usefulness of serial chocolate competition as a test of dominance is discussed.

Animals↗
PubMed1986

Amnesic and anxiolytic effects of intravenous diazepam in dental anxiety.

The effects of intravenous administration of diazepam (average 20 mg) on learning, performance and mood were assessed in dental patients. These patients required sedation due to excessive anxiety in a dental situation, or because they were to undergo stressful surgery. On a verbal learning task, subjects recalled and recognized significantly fewer words from a list presented after drug administration than from a list presented prior to drug administration, when tested at the end of the treatment period. When tested after treatment, subjects recognised few of a series of picture postcards that had been presented to them during the course of treatment. Subjects showed no significant impairments after diazepam treatment on digit-symbol substitution, symbol copying or number cancellation tasks compared to pre-treatment scores; however, there was a small but significant reduction in the number of finger-taps made. Mood-rating scales showed significant increases in sedation and well-being after diazepam treatment compared to pre-treatment scores, and also a significant reduction in anxiety levels. This study shows that the amnesic effects of diazepam are present in a "real-life" stress situation.

Anti-Anxiety Agents↗
PubMed1985

Triazolobenzodiazepines antagonize the effects of anxiogenic drugs mediated at three different central nervous system sites.

The ability of the triazolobenzodiazepines to antagonize the anxiogenic effects of three different compounds in the social interaction test was investigated. The compounds were selected for their different sites of action in the central nervous system: FG 7142, acting at the beta-carboline site on the gamma-aminobutyric acid-benzodiazepine receptor complex; pentylenetetrazole, acting at the picrotoxin site on this complex, and yohimbine, an alpha 2-adrenoceptor antagonist. Adinazolam (5 mg/kg) and U-43,465 (32 mg/kg) were able to antagonize the anxiogenic effects of all three compounds, unlike classical 1,4-benzodiazepines, that are not able to antagonize the effects of yohimbine. The results are discussed in terms of the anti-panic activity of the triazolobenzodiazepines.

Alprazolam↗
PubMed1985

Are the anxiogenic effects of yohimbine mediated by its action at benzodiazepine receptors?

Yohimbine, which has activity both at alpha 2-adrenoreceptors and benzodiazepine receptors in the CNS, had an anxiogenic action (1.25-2.5 mg/kg) in the social interaction test in rats. This effect was reversed by the alpha 2-adrenoceptor agonist clonidine (0.01 mg/kg), but not by the benzodiazepine receptor agonist chlordiazepoxide (5-10 mg/kg) or the antagonist Ro 15-1788 (10 mg/kg). These results suggest that the anxiogenic effects of yohimbine are not attributable to its low affinity effects at benzodiazepine receptors but to its alpha 2-adrenoceptor antagonist activity.

Animals↗
PubMed1985

The sedative effects of CL 218,872, like those of chlordiazepoxide, are reversed by benzodiazepine antagonists.

The effects of CL 218,872, initially classified as a non-sedative anxiolytic, were investigated and compared with those of chlordiazepoxide in the holeboard. The ability of two drugs that antagonise the effects of benzodiazepines, CGS 8216 and Ro 15-1788, to reverse the effects of CL 218,872 and chlordiazepoxide were also investigated, to see whether their effects might be mediated via benzodiazepine receptors. CL 218,872 (10 mg/kg) was found to be significantly sedative in both mice and rats (i.e., both locomotor activity and head-dipping were significantly decreased). In mice, the effects of CL 218,872 and of chlordiazepoxide were very similar over a range of doses, except that the stimulatory effect seen with low doses of chlordiazepoxide on head-dipping just failed to reach significance with CL 218,872. This study is in agreement with recently published results from different tests showing that sedative effects can be obtained with doses of CL 218,872 that are low and not much higher than those leading to anxiolysis. The sedative effects of both CL 218,872 (10 mg/kg) and chlordiazepoxide (20 mg/kg) were significantly reversed by RO 15-1788 (10 and 20 mg/kg) and CGS 8216 (10 mg/kg), suggesting that their effects are mediated via benzodiazepine receptors. The increase in head-dipping seen with chlordiazepoxide (2.5 mg/kg) was also reversed by RO 15-1788 and CGS 8216.

Animals↗
PubMed1985

Long-lasting anticonvulsant effects of diazepam in different mouse strains: correlations with brain concentrations and receptor occupancy.

There were marked strain differences in the duration of the protective effects of diazepam against the convulsant actions of penylenetetrazole and picrotoxin in mice. In no case was significant protection found at 12 h or longer, regardless of whether the incidence of or the latencies to myoclonus or tonic-clonic convulsions were considered. These behavioural differences could not be explained simply in terms of strain differences in benzodiazepine metabolism or in percent of receptor occupancy, as determined by the fractional displacement of 3H-flunitrazepam binding in vivo. It is suggested that there might be strain differences in the percent of receptor occupancy needed in order to produce an anticonvulsant effect.

Animals↗
PubMed1985

The anxiogenic action of RO 5-4864 in the social interaction test: effect of chlordiazepoxide, RO 15-1788 and CGS 8216.

RO 5-4864 (20 mg/kg), a benzodiazepine with high affinity for peripheral-type benzodiazepine binding sites in rat kidney and brain, but not for the "classical" CNS sites, reduced the time spent by pairs of rats in active social interaction, without reducing locomotor activity, possibly reflecting an anxiogenic action. This anxiogenic effect was not reversed by chlordiazepoxide (5 or 10 mg/kg) given acutely, but was reversed by chlordiazepoxide (5 mg/kg) given for 5 days prior to testing. RO 15-1788 (10 mg/kg), a drug that antagonises several effects of benzodiazepines but has little affinity for peripheral-type sites, had no action on the reduction in social interaction induced by RO 5-4864. However, CGS 8216 (10 mg/kg) which also antagonises the effects of benzodiazepines and has little affinity for RO 5-4864 recognition sites, significantly enhanced the reduction in social interaction caused by RO 5-4864, and the combination produced a significant decrease in locomotor activity. These results are discussed in terms of possible sites of action of RO 5-4864 on the GABA-benzodiazepine receptor complex.

Animals↗
PubMed1985

Anticonvulsant effects of chronic treatment with phenytoin against pentylenetetrazole-induced seizures in the mouse.

Acute administration of phenytoin (40 and 75 mg/kg) was unable to counteract seizures induced by pentylenetetrazole and even prolonged them in some cases. These prolonged seizures remained with chronic (10 days) treatment but an anticonvulsant effect of phenytoin (40 and 75 mg/kg) also emerged, shown by a decrease in the incidence of seizures. This latter effect could be detected even 24 hr after the last dose. Both acute and chronic treatment with phenytoin (40 or 75 mg/kg) were able to enhance anticonvulsant efficacy of diazepam against pentylenetetrazole-induced seizures. The mechanisms underlying these three independent effects of phenytoin and their clinical relevance are discussed.

Animals↗
PubMed1985

The effects of putative anxiolytic compounds (PK 8165, PK 9084 and tracazolate) on the rat corticosterone response.

The effects were investigated of three putative anxiolytics, thought to act at the GABA-benzodiazepine receptor complex, on basal corticosterone and novelty-induced rise in plasma corticosterone concentrations. The two phenylquinolines, PK 8165 and PK 9084, increased basal concentrations, but reduced the novelty-induced rise in corticosterone; these actions resemble those found with high doses of benzodiazepines. Tracazolate, a pyrazolopyridazine that enhances the binding of benzodiazepines to their receptors, was without significant effect in either situation.

Animals↗
PubMed1985

The effects of putative anxiogenic compounds (FG 7142, CGS 8216 and Ro 15-1788) on the rat corticosterone response.

The effects of FG 7142, CGS 8216 and Ro 15-1788, three compounds that are believed to produce anxiety by an action at benzodiazepine receptors in the CNS, are investigated on the plasma corticosterone concentrations in the rat both in the home cage and after exposure to novelty stress. FG 7142 (5 mg/kg) and CGS 8216 (10 mg/kg), but not Ro 15-1788 (4 or 10 mg/kg) increased basal corticosterone levels in the home cage, and all three compounds potentiated the increase in corticosterone concentrations observed after exposure to a novel environment. The relationship between the effects of drugs on corticosterone concentrations and on anxiety is considered in the light of these results.

Animals↗
PubMed1985

The effects of PK 11195, a ligand for benzodiazepine binding sites, in animal tests of anxiety and stress.

PK 11195 (1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinolinecarboxami de, a potent ligand for peripheral benzodiazepine binding sites, was unable to reverse the anxiogenic effects of Ro 5-4864 (chlorodiazepam) in the social interaction test or in the punished drinking test. However, at 90 mg/kg PK 11195 also reduced social interaction, indicating an anxiogenic effect. Both PK 11195 (30-120 mg/kg) and Ro 5-4864 (20-60 mg/kg) significantly increased the plasma corticosterone concentrations of rats left in their home cages after injection, and in those placed in novel apparatus. Because both drugs had effects in the same direction and because the doses were far higher than those needed to saturate the peripheral receptor, it is unlikely that these behavioural actions are mediated by peripheral benzodiazepine binding sites. It is suggested that the effect of PK 11195 could even be mediated by the classical CNS benzodiazepine binding sites.

Animals↗
PubMed1985

Chlordiazepoxide enhances the anxiogenic action of CGS 8216 in the social interaction test: evidence for benzodiazepine withdrawal?

The benzodiazepine receptor 'inverse agonist' CGS 8216 has a specific anxiogenic action in the social interaction test that cannot be reversed by other compounds acting at the benzodiazepine site: Ro 15-1788, FG 7142 or beta-CCE. We tried to reverse the anxiogenic effect with chlordiazepoxide, which is able to antagonise the anxiogenic effects of several other compounds acting at benzodiazepine or related sites. Chlordiazepoxide given acutely (10-20 mg/kg) was unable to antagonise the anxiogenic action of CGS 8216 (5-10 mg/kg); instead there was a tendency to enhance its effects. The effects of chlordiazepoxide after 5 days pretreatment were then assessed, since chronic treatment is necessary to reverse the anxiogenic actions of Ro 15-1788 and Ro 5-4864. At 5 mg/kg chronically, chlordiazepoxide was unable to antagonise the anxiogenic effect of CGS 8216, and at 20 mg/kg there was a significant enhancement of the effects of CGS 8216 on social interaction without an effect on locomotor activity. These results are discussed in terms of withdrawal from benzodiazepine treatment.

Animals↗
PubMed1985

Effects of the beta-carboline, FG 7142, in the social interaction test of anxiety and the holeboard: correlations between behaviour and plasma concentrations.

The behavioural effects of the beta-carboline FG 7142 were investigated in the social interaction test of anxiety and the holeboard test of exploration and locomotor activity. FG 7142 (5-20 mg/kg) produced a significant decrease in the time spent in social interaction by pairs of rats, without an accompanying decrease in motor activity. This anxiogenic effect was highly correlated with the plasma concentrations of FG 7142 for the rats receiving 5 and 10 mg/kg doses, but not for those receiving the 20 mg/kg dose. In the holeboard, FG 7142 had no effect on exploratory head-dipping at the doses tested, but selectively reduced locomotor activity and the number of rears. The profile of FG 7142 in these tests is compared with those of the beta-carbolines, B-CCE and B-CCP.

Animals↗
PubMed1985

Benzodiazepines and behavior.

This article sets the background for the following series of articles on the behavioral actions of drugs acting at the GABA-benzodiazepine receptor complex. The articles provide detailed analyses of particular behaviors and emphasise the danger of interpreting all behavioral effects in terms of anxiety. What also emerges clearly from several of the articles is that any agonist/inverse agonist classification is test-dependent and that global categorisation is not possible for many of the novel compounds.

Animals↗