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S E File

Publications and source records attributed to S E File.

At least 307 records · Page 17Linked to original sources
PubMed1979

A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants.

The effects of minor tranquilisers and of stimulant drugs were studied in the Social Interaction test of anxiety in which the illuminance and unfamiliarity of the test arena are manipulated. Acute administration of sodium phenobarbitone (25 mg/kg) was without effect. Acute administration of sodium phenobarbitone (35 mg/kg) and of meprobamate (60 mg/kg) produced sedation: both locomotor activity and social interaction were reduced. On the other hand, amphetamine sulphate (2 mg/kg) and caffeine citrate (20 mg/kg) reduced social interaction, but increased locomotor activity. Chronic administration dissociated the pattern of results produced by sodium phenobarbitone (35 mg/kg) from that produced by flurazepam (0.5 mg/kg). With chronic treatment (5 days) neither drug reduced motor activity, but whereas phenobarbitone increased social interaction regardless of the test illuminance and unfamiliarity, the increase produced by flurazepam was limited to the more stressful test conditions, i.e., when the arena was unfamiliar or brightly lit.

Amphetamine↗
PubMed1979

Ascending 5-HT pathways and behavioural habituation.

Microinjections of 5,7 -dihydroxytryptamine into both the dorsal and median raphe nuclei resulted in 70-85% depletions in striatal and hippocampal 5-HT concentrations but did not affect habituation of orienting in the lick-distraction test, habituation of activity in an open-field or habituation of exploration in the holeboard test. Lesioned animals were hypoactive in the latter two tests and defaecated more than control rats in the open-field suggesting an increase in emotionality or fear. Rats with selective 5,7 -dihydroxtryptamine lesions of either the dorsal or the median raphe nucleus also showed no impairment of habituation of orienting or exploration. However, median raphe lesioned animals were hyperactive at some stages of the holeboard test. In contrast to previous studies, the results suggest intact ascending 5-HT pathways are not necessary for behavioural habituation of orienting, activity or exploration. Rather, 5-HT neurones may be involved in modulation of activity or responsiveness to aversive environments.

Acoustic Stimulation↗
PubMed1979

Evidence that piracetam has an anxiolytic action.

In the social interaction test of anxiety Piracetam (100 mg/kg) had an anxiolytic profile very similar to that seen after 5 days of administration of chlordiazepoxide (5 mg/kg). Piracetam (50-300 mg/kg) produced no signs of sedation and it was therefore suggested that it might be a non-sedative anxiolytic drug. Piracetam (100 mg/kg) produced significantly higher cortical concentrations of 5-hydroxytryptamine and lower concentrations of 5-hydroxyindoleacetic acid, indicating a reduced 5-HT turnover. There were no drug-induced changes in noradrenaline or dopamine in any brain region, either with or without pretreatment with alpha-methylparatyrosine. The cortical concentrations of 7 amino acids were measured and were unchanged by treatment with Piracetam.

Amino Acids↗
PubMed1979

5,7-dihydroxytryptamine lesions of dorsal and median raphé nuclei and performance in the social interaction test of anxiety and in a home-cage aggression test.

Micro-injections of the neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus produced a behavioural profile in the social interaction test of anxiety similar to that seen in rats treated chronically with benzodiazepines. Neurotoxin injections into the median raphé nucleus did not produce a profile significantly different from that of the controls. In the control rats and in the rats with lesions of the median raphé nucleus, ACTH1-24 (corticotrophin) significantly reduced active social interactions, whereas it was without effect on the rats with lesions of the dorsal raphé nucleus. In the home-cage intruder test, the median raphé-lesioned rats submitted less to the intruder and stood and jumped on him more often than did the controls. The dorsal raphé-lesioned rats showed significantly fewer interactions of all kinds, compared with control rats when an intruder was placed in their home cages.

5,7-Dihydroxytryptamine↗
PubMed1979

Corticosterone -- an anxiogenic or an anxiolytic agent?

Corticosterone (3--12 mg kg-1, i.p., giving rise to plasma corticosterone concentrations from 26.7 to 89.0 micrograms/100 ml) failed to have a significant anxiogenic action. Instead, corticosterone (3 mg kg-1) had a significant anxiolytic effect in the social interaction test of anxiety. Adrenalectomized rats had very low levels of social interaction; but adrenalectomized rats that had been given replacement corticosterone therapy did not differ from the sham-operated controls. Thus, corticosterone appears to have the opposite effect to that previously reported for ACTH. Possible mechanisms for the observed results are discussed.

Adrenalectomy↗
PubMed1978

The locus coeruleus noradrenergic system--evidence against a role in attention, habituation, anxiety and motor activity.

Lesions of the locus coeruleus system were induced by combined stereotaxic injections of 6-OH-dopamine to the ascending fibres and just lateral to the locus coeruleus itself, to deplete the noradrenaline content of both the cerebral and cerebellar cortices. A group of rats with cortical noradrenaline concentrations of less than 30 ng/g were compared with a group with lesser destruction of the system (mean noradrenaline concentration 71 +/- 44 ng/g) and with controls (mean noradrenaline 347 +/- 58 ng/g). Lesioned rats showed normal motor activity and exploration (assessed with a holeboard) and showed normal habituation of these behaviours. The lesioned rats gave no evidence of increased susceptibility to distracting auditory stimuli whilst licking for water, and the groups did not differ in their rate of habituation to these stimuli, or in dishabituation. In a social interaction test, lesioned animals showed a decrease in social contacts in an unfamiliar situation (interpreted as a response to anxiety) of similar magnitude to that seen in the control group. In this test, lesioned animals engaged in more 'aggressive' behaviour (boxing and wrestling) than did the controls. These findings are incompatible with hypotheses that the locus coeruleus system is an integral part of the physiological mechanisms which control gross motor behaviour, attention, habituation or anxiety. Together with previous findings with the benzodiazepines, the results with the social interaction test make it unlikely that the benzodiazepines exert their anxiolytic effects by inhibiting the locus coeruleus system.

Acoustic Stimulation↗
PubMed1978

Exploration, distraction, and habituation in rats reared in isolation.

Rats reared in isolation have been reported to show increased motor activity; the purpose of the present experiment was to establish whether they also show enhanced exploratory and orienting responses. Rats were reared in isolation or in social groups from Day 20 to Day 45. Subgroups of each rearing condition were either left undisturbed, received daily handling, or received daily handling and were given objects in their cages. From Day 45 all the rats were rehoused in groups of 6, and testing began at Day 73. In a 1st test exploration was measured by the number of contacts with objects placed in the home cage; and a 2nd test exploration was measured by responses to a holeboard; and in a 3rd test orienting was measured by the distraction produced by the presentation of a tone. When tested in novel situations, in contrast to their enhanced motor activity, isolates showed reduced exploration and orienting. This may have been due to a discrepancy between their adaptation level (established during rearing) and their current level of sensory input. In all the tests the isolates showed normal habituation, both within sessions and between sessions. An inability to habituate is not, as has been claimed, a general characteristic of isolates.

Age Factors↗
PubMed1978

The ontogeny of exploration in the rat: habituation and effects of handling.

Exploration, measured by head-dipping in a holeboard, was tested in male rats at 16, 21, 28, 56, and 84 days of age. Head-dipping increased with increasing age from Day 16 to Day 84, and so did the number of rears made. At all ages handled rats showed more head-dipping and made more rears than did their unhandled litter-mates. The age differences in exploration cannot be explained by different patterns of habituation: rats showed significant within-session habituation of head-dipping at all ages tested (Days 16, 21, and 28). Day 16 rats also showed significant between-session habituation.

Age Factors↗
PubMed1978

Exploration in immature rats: effects of drugs.

The effects of d-amphetamine (4 mg/kg), scopolamine (1 mg/kg), methylscopolamine (1 mg/kg), and parachlorophenylalanine (400 mg/kg) on exploration were studied in male rats at 16, 21, and 28 days of age. Amphetamine elicited stereotypy at all ages tested, reduced exploration (measured by the time spent head-dipping during a 10-min trial in a holeboard) from Day 21, but did not significantly increase rearing at the ages tested. (Reduced head-dipping, accompanied by stereotypy, is the pattern of results previously seen in adult rats with this dose of amphetamine.) An interesting difference emerged with scopolamine, which reduced head-dipping at all the ages tested, whereas in adults it produced an increase. The age-related difference in drug effects suggests that muscarinic pathways are functioning from Day 16, but that the system concerned with exploration functions differently in mature and immature rats. Both scopolamine and methylscopolamine reduced rearing which suggests that the change is due to peripheral actions of the drugs. Parachlorophenylalanine, which decreases serotonin levels, increased head-dipping, as it has been found to do in adult rats.

Aging↗
PubMed1978

ACTH, but not corticosterone impairs habituation and reduces exploration.

The habituation of an orienting response to auditory stimuli was impaired in rats by the administration of ACTH1-24. This impairment is unlikely to be due to the action of corticosterone because of the time course of the effect, because injected corticosterone had no effect on hibituation and because the peptide fragment ACTH4-10, which does not release corticosterone, also impaired habituation. Both ACTH1-24 and ACTH4-10 reduced the level of exploration measured in a holeboard, but corticosterone had no significant effect. However ACTH did not impair habituation and exploration, thus providing further evidence that there are different mechanisms underlying habituation of orienting and habituation of exploration.

Adrenocorticotropic Hormone↗
PubMed1978

Can social interaction be used to measure anxiety?

1 Pairs of male rats were placed in a test box for 10 min and the time they spent in active social interaction was scored. Maximum active interaction was found when the rats were tested under low light in a box with which they were familiar. When the light level was increased or when the box was unfamiliar active social interaction decreased. 2 Exploration (time spent sniffing objects) decreased in the same way in relation to test conditions as did social interaction. As these decreased, defecation, and freezing increased. 3 Anosmic controls showed that the decrease in social interaction across test conditions could not be attributed to olfactory changes in the partner. 4 Chlordiazepoxide (5 mg/kg) given chronically prevented or significantly reduced the decrease in social interaction that occurred in undrugged rats as the light level or the unfamiliarity of the test box was increased. Controls showed that this effect could not be entirely attributed to chlordiazepoxide acting selectively to increase low levels of responding. 5 The effect of chronic chlordiazepoxide contrasts with its action when given acutely; in the latter case it has only sedative effects. 6 Whether this test can be used as an animal model of anxiety is discussed and this test is compared with existing tests of anxiety.

Animals↗
PubMed1978

Studies on the role of ACTH and of 5-HT in anxiety, using an animal model.

The effects of ACTH (5 & 7.5 microgram/100 g) were studied using a new animal model of anxiety. ACTH had an anxiogenic effect that was maximal during a 10 min test period starting 3 min after injection. The behavioural effects of ACTH were counteracted by chronic administration of chlordiazepoxide (5 mg kg-1 for 5 days) and by acute administration of ethanol (0.4 g kl-1). These anxiolytic drugs decreased the turnover of 5-HT in the midbrain, hypothalamus and cerebral cortex, whereas ACTH increased 5-HT turnover in the midbrain and hypothalamus. Is it therefore proposed that anxiety results from the action of ACTH, possibly on 5-HT pathways in the midbrain and hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1977

Effects of parachlorophenylalanine and amphetamine on habituation of exploration.

Parachlorophenylalanine (PCPA, 400 mg/kg) retarded the habituation of exploration in the rat recorded over 3 successive days. A more detailed analysis showed that this was not due to any retention deficit, but was secondary to an impairment of habituation within each session. PCPA also disrupted the response of rats to a change of stimuli. (+)amphetamine (4 mg/kg) prevented exploration in the rat and a 2 mg/kg dose reduced exploration and impaired within-session habituation. (+)amphetamine (1 mg/kg) in mice impaired within-session habituation, without significantly reducing exploration. The nature of the deficits produced by these 2 drugs is discussed.

Animals↗