Search PubMed⌕ Search

Biomedical subjects

R G Lister

Publications and source records attributed to R G Lister.

At least 37 records · Page 2Linked to original sources
PubMed1989

Behavioral effects of alpha 2 adrenoceptor antagonists and their interactions with ethanol in tests of locomotion, exploration and anxiety in mice.

The behavioral effects of two highly selective alpha 2-adrenoceptor antagonists, atipamezole and idazoxan, were investigated in mice using the plusmaze test of anxiety and the holeboard test of directed exploration and locomotor activity. No anxiogenic effect, as assessed by the tendency to enter the closed as opposed to open arms of the plusmaze, was noted for either drug at any dose tested. Neither were there any significant effects on locomotor activity or directed exploration (head-dipping) in the holeboard, or total plusmaze arm entries at any dose of either drug. The co-administration of either atipamezole or idazoxan had no effect on either the anxiolytic effect of ethanol (2 g/kg) or its locomotor stimulant effect in the holeboard. Atipamezole (1.0 and 3.0 mg/kg) significantly reversed the ethanol-induced reduction in exploratory head-dipping; a similar trend was seen for idazoxan. There was also a significant potentiation of the ethanol-induced increase in the number of total arm entries made on the plusmaze caused by 1.0 mg/kg (but not 3.0 mg/kg) atipamezole and both 0.3 and 1.0 mg/kg idazoxan. The results suggest that some of the behavioral effects of ethanol can be reversed by alpha 2-adrenoceptor antagonists whilst others are unchanged.

Adrenergic alpha-Antagonists↗
PubMed1989

Attenuation of ethanol intoxication by alpha-2 adrenoceptor antagonists.

The interaction of a highly potent and selective alpha-2 adrenoceptor antagonist, atipamezole with ethanol was investigated in tests assessing a number of ethanol's behavioral effects. Atipamezole antagonized ethanol's effects on directed exploration in a holeboard test, reduced observer-rated intoxication and also reduced the duration of loss of righting reflex caused by ethanol. Similar effects were produced by another alpha-2 adrenoceptor antagonist idazoxan. The magnitude of the effects was comparable to that produced in the same animal models by the imidazodiazepine Ro 15-4513, which antagonizes ethanol by an action at central benzodiazepine receptors. Whereas Ro 15-4513 possesses marked behavioral effects on its own, atipamezole is comparatively inactive in all paradigms so far tested. The data suggest that alpha-2 adrenoceptors can play an important role in modulating the intoxicating effects of ethanol.

Adrenergic alpha-Antagonists↗
PubMed1989

Effects of caffeine on social behavior, exploration and locomotor activity: interactions with ethanol.

The effects of caffeine and its interaction with ethanol were examined in a test of social behavior and a holeboard test of exploration and locomotion. Male mice were injected i.p. with 15, 30 or 60 mg/kg caffeine alone or in combination with 2 g/kg ethanol. The animals were then put in pairs into a familiar arena, or examined individually in the holeboard. Only the highest dose of caffeine (60 mg/kg) had a significant effect on the time spent in social interaction and motor activity in the social behavior test: both measures were reduced. The duration and frequency of avoidance-irritability behavior was dose-dependently increased by caffeine. In the holeboard, caffeine caused a dose-dependent increase in locomotor activity. 30 mg/kg caffeine reversed the ethanol-induced reduction of time spent in social interaction, and 60 mg/kg caffeine antagonized the ethanol-induced increase in locomotor activity in both the social behavior and holeboard tests. Caffeine's effects on ethanol-induced behavioral changes are compared with those of other drugs.

Aggression↗
PubMed1989

Interactions of alpha 2-adrenoceptor antagonists with medetomidine and with ethanol in a holeboard test.

The effects of two selective alpha 2-adrenoceptor agonists (clonidine and medetomidine) and antagonists (atipamezole and idazoxan) were examined in the holeboard test. The interactions of the two antagonists with ethanol were also investigated. Atipamezole (0.1-3.0 mg/kg) and idazoxan (0.01-0.3 mg/kg) were without effect on either directed exploration or locomotor activity in the holeboard test, whereas clonidine (0.003-0.1 mg/kg) and medetomedine (0.003-0.1 mg/kg) were sedative. Atipamezole (1-3 mg/kg) and idazoxan (0.3-1.0 mg/kg) reversed the behavioral effects of 0.1 mg/kg of medetomidine. When administered with ethanol (2 g/kg), atipamezole (1-3 mg/kg) showed a significant antagonism of the ethanol-induced reduction in exploratory head-dipping: no change in the locomotor stimulant properties of ethanol was seen. A similar trend was seen for exploration after a combination of idazoxan (1-3 mg/kg) with 2 g/kg ethanol; however, the 3 mg/kg dose attenuated the locomotor stimulant effect. Both antagonists caused a dose-related reduction in the increase in head-dipping seen after administration of 1 g/kg of ethanol, without any effect on the locomotor stimulant effect of this dose. These results suggest mediation of alpha 2-adrenoceptors in some of the behavioral effects of ethanol.

Adrenergic alpha-Agonists↗
PubMed1989

Reduction of the intoxicating effects of ethanol by drugs acting at the benzodiazepine-GABA receptor complex.

The ability of the benzodiazepine receptor partial inverse agonists Ro 15-4513, Ro 15-3505 and FG 7142, and the picrotoxin site ligands pentylenetetrazole and Ro 5-3663 to reduce ethanol-induced intoxication were investigated. Ro 15-4513 (0.3-3 mg/kg), Ro 15-3505 (3 mg/kg), pentylenetetrazole (20 and 25 mg/kg) and Ro 5-3663 (4 mg/kg) all significantly attenuated the intoxicating effects of ethanol. In contrast, FG 7142 (20 and 40 mg/kg) failed to reduce ethanol intoxication, but reversed the effect of Ro 15-4513. This pattern of results differs from that obtained using other behavioral paradigms. Since drugs which reduce the effects of GABA generally reduce the intoxicating effects of ethanol, it is suggested that the beta-carbolines may be unusual in their interaction with ethanol.

Animals↗
PubMed1989

Effect of isolation on brain monoamines and the behavior of mice in tests of exploration, locomotion, anxiety and behavioral 'despair'.

We have recently found that, besides an increase in aggression, isolation increases social interaction in NIH Swiss mice. In the present study the effect of isolation in other behavioral paradigms and their relation to brain monoamine concentrations were investigated. Mice, isolated for 0-20 days, were tested in the holeboard test of exploration and locomotor activity, the plus-maze test of anxiety, and Porsolt's swim test of behavioral 'despair.' Isolation reduced exploratory head-dipping, increased locomotor activity and increased the preference of mice for the open arms of the plus-maze. The immobility time in the swim test was shortened in mice isolated for 2 or 5 days, suggesting an improved ability to cope with stressful situations. Monoamine assays failed to show significant changes in the noradrenaline, dopamine, HVA, 5-HT or 5-HIAA contents in the amygdala, hypothalamus, hippocampus or brain stem. The results indicate that isolation of NIH Swiss mice for less than three weeks induces several behavioral changes, but is not particularly stressful.

Animals↗
PubMed1989

Effects of ethanol on fight- or swim-stressed mice in Porsolt's swim test.

The effects of ethanol in Porsolt's swim test on mice preexposed to fight- or swim-stressors were investigated. The control mice did not change their behavior in the swim test after an acute injection of 0.4 or 0.8 g/kg ethanol; 1.2 g/kg ethanol increased their immobility in one but not in another experiment. The mice exposed to continuous fight-attacks in their home cage by one dominant mouse shortened immobility after 0.8 g/kg ethanol as well as tended to shorten it after 0.4 g/kg ethanol. The mice that were forced to swim in the water twice before the actual swim test responded to 0.4 g/kg ethanol by shortening immobility; 0.8 g/kg tended to have the same effect; 1.2 g/kg ethanol just failed to lengthen immobility of the fight-stressed mice and had no effect on the swim-stressed mice. Because antidepressant drugs decrease and stressors increase immobility in the swim test, the test may serve as a putative animal model of depression. The present findings showed that low doses of ethanol reverse lengthened immobility of mice preexposed to a stressor. This suggests that ethanol either has antidepressant-like properties, or it improves animal's ability to cope with a stressful situation, or both.

Aggression↗
PubMed1989

Does directed exploration influence locomotor activity in a holeboard test?

The effects of three drugs, chosen for their differential effects on directed exploration and locomotion (ethanol, caffeine, and FG 7142), were examined on the locomotor activity of mice in a holeboard apparatus containing either a solid floor or one with four holes in it. The dose-related effect of all three drugs on locomotor activity was not changed by the presence of the holes, although activity was slightly higher when a solid floor was used. The results indicated that the two measures can vary independently and that the directed exploration component (head-dipping) of the holeboard test does not significantly influence the locomotor activity component.

Animals↗
PubMed1989

Effect of ethanol on the social behavior of group-housed and isolated mice.

The interaction between isolation and the response to ethanol was investigated with a social behavior test and a loss of righting reflex paradigm. The time a pair of mice spent in active social interaction, aggressive behavior, and avoidance-irritability showed an isolation-related increase, while locomotor activity was not affected by 0-10 days of isolation. Ethanol (0.8 g/kg) reduced the social interaction time in mice isolated for 10 days and 2.0 g/kg ethanol reduced it in all groups. Ethanol induced a locomotor stimulatory effect both in group-housed and isolated animals. An aggression-inducing effect of 0.8 g/kg ethanol was observed only in mice isolated for 5 days, while mice isolated for 10 days reduced their aggressive behavior after this dose of ethanol. The loss of righting reflex after 3.5 g/kg ethanol did not appear to vary with isolation. The results suggest that isolation alters some effects of ethanol qualitatively (e.g., its effects on aggressive behavior) but leaves other effects (e.g., its locomotor stimulant and hypnotic effects) unchanged.

Aggression↗
PubMed1988

RO 15-4513 and FG 7142 reverse the reduction in social behavior caused by ethanol in mice.

Ethanol (2 g/kg) reduces the time spent in social interaction and increases locomotor activity of pairs of NIH Swiss mice. This study examined whether two benzodiazepine receptor inverse agonists, RO 15-4513 (3 mg/kg) and FG 7142 (30 mg/kg) are able to reverse these effects. Neither drug alone altered social behavior, but both significantly attenuated the effect of ethanol on social interaction. They did not affect the ethanol-induced increase in motor activity. Benzodiazepine receptor inverse agonists thus appear capable of antagonizing some, but not all of the behavioral effects of ethanol in this paradigm.

Aggression↗
PubMed1988

RO 15-4513 does not protect rats against the lethal effects of ethanol.

In two separate research centres the ability of RO 15-4513 to protect rats against the lethal effects of ethanol (7.5 and 15 g/kg) was investigated. In neither study did RO 15-4513 offer protection against ethanol-induced lethality or the loss of righting reflex caused by these doses of ethanol. These data fail to replicate the results of an earlier report and suggest that RO 15-4513 is unlikely to be clinically useful treating acute severe ethanol toxicity.

Animals↗
PubMed1988

Clinical relevance of effects of benzodiazepines on learning and memory.

The effects of benzodiazepines on learning and memory are examined in the various clinical situations in which these drugs are used. Alterations in performance arising from the conditions for which benzodiazepines are prescribed are also considered. Current evidence indicates that, in anxious patients, as in normal volunteers, benzodiazepines impair the acquisition of new information (episodic memory). Although some tolerance may develop to these impairments, deficits are observed even after patients have been taking their medication chronically. Like amnesic patients, benzodiazepine-treated subjects may be unaware of their impaired ability to learn. The effects of the impairments on behavioral psychotherapies are considered.

Anti-Anxiety Agents↗
PubMed1988

The effects of novelty, isolation, light and ethanol on the social behavior of mice.

The social behavior of pairs of male NIH Swiss mice was assessed under a variety of experimental conditions. Increasing periods of isolation increased both the total time spent in social interaction and also increased the incidence of aggressive behavior. Familiarity with the testing arena tended to increase social behavior, but the magnitude of this effect was considerably less than that previously observed in rats. High light levels reduced social interaction. Ethanol (0.8-2.4 g/kg) caused a dose-related decrease in the total time spent in social interaction, a biphasic effect on aggressive behavior and a dose-related increase in locomotor activity. While the social interaction test in this form may not be a suitable model of anxiety in NIH Swiss mice, it should provide a useful method of assessing drug effects and investigating genetic influences on social and aggressive behavior.

Aggression↗
PubMed1988

Behavioral interactions of fluoxetine and other 5-hydroxytryptamine uptake inhibitors with ethanol in tests of anxiety, locomotion and exploration.

The 5HT uptake inhibitor fluoxetine had no effect on motor activity or directed exploration (head-dipping) in a holeboard test or in an elevated plusmaze test of anxiety. Fluoxetine (20 mg/kg) attenuated the anxiolytic effect of a 2.4 g/kg dose of ethanol in the plusmaze but failed to alter ethanol's effects on exploratory head-dipping or locomotion. This interaction did not seem directly related to fluoxetine's 5HT uptake inhibiting properties because it was not observed with other 5HT uptake inhibitors (fluvoxamine and citalopram). Desipramine, which predominantly inhibits noradrenaline uptake, also failed to show effects similar to those of fluoxetine.

Animals↗
PubMed1988

Time course of ethanol's effects on locomotor activity, exploration and anxiety in mice.

The time course of the effects of two doses of ethanol on exploration, locomotor activity and anxiety were investigated using the holeboard and plus-maze tests. In an 8 min holeboard test the lower (1.2 g/kg) dose increased both exploration and locomotor activity 0.5 h after ethanol administration whereas the higher (2.4 g/kg) dose decreased exploration but caused an even greater increase in locomotor activity. This activity increase was also seen 1 h post-administration. In the plus-maze test both doses showed an increased number of arm-entries 0.5 h and 1 h after administration but only the 2.4 g/kg dose caused anxiolytic effects persisting for over 2 h. The results add further support to the notion that the behavioral effects of ethanol vary with dose, time of administration and the behavioral measure taken.

Animals↗
PubMed1988

Behavioral interactions between ethanol and imidazodiazepines with high affinities for benzodiazepine receptors.

The intrinsic effects of two imidazodiazepines RO 15-3505 and RO 17-1812 on the behavior of mice in a holeboard test were investigated. The interactions of these two drugs with ethanol were also studied. RO 15-3505 (0.75-6.0 mg/kg) failed to significantly alter either exploratory head-dipping or locomotor activity when administered alone but doses of 0.75 and 1.5 mg/kg reversed the reduction in the number of head-dips caused by ethanol (2 g/kg) and partially reversed ethanol's locomotor stimulant action. In contrast, RO 17-1812 (0.75-6.0 mg/kg) increased locomotor activity when administered alone, and enhanced the reduction in exploration caused by ethanol. Neither RO 15-3505 nor RO 17-1812 altered blood alcohol concentrations suggesting a pharmacodynamic basis for these interactions. The results suggest that in the holeboard test the interactions of imidazodiazepines with ethanol are related to the nature of their interaction with benzodiazepine receptors, inverse agonists antagonising and agonists enhancing ethanol's effects on exploration.

Animals↗
PubMed1988

Interactions of three benzodiazepine receptor inverse agonists with ethanol in a plus-maze test of anxiety.

The effects of RO 15-4513, RO 15-3505 and FG 7142 on the anxiolytic properties of ethanol in mice were investigated using the plus-maze test of anxiety. Before being tested on the plus-maze, the mice were tested in a holeboard apparatus. All three inverse agonists attenuated the reduction in exploration caused by ethanol in the holeboard test. In the plus-maze, only RO 15-4513 and FG 7142, which possess anxiogenic properties when administered alone, attenuated ethanol's anxiolytic effect. RO 15-3505, which alone had no effect on anxiety, failed to significantly reduce ethanol's anxiolytic effect. Neither RO 15-4513 nor FG 7142 reduced the increase in the total number of arm entries caused by ethanol. These data indicate that the interaction between ethanol and benzodiazepine receptor ligands depends both on the intrinsic properties of the ligands and the behavior under investigation.

Animals↗