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Biomedical subjects

M J Durcan

Publications and source records attributed to M J Durcan.

At least 37 records · Page 2Linked to original sources
PubMed1990

Behavior of streptozotocin-diabetic mice in tests of exploration, locomotion, anxiety, depression and aggression.

The present study examined behavior of streptozotocin-diabetic mice in Porsolt's swim test, a putative animal model of depression, in the holeboard test of exploration and locomotor activity, in the plus maze test of anxiety, and in the resident-intruder paradigm of aggression. Two weeks after an IP injection of 200 mg/kg streptozotocin, which caused a 20% weight loss and increased fluid consumption and urination, male NIH Swiss mice were found to show lengthened duration of immobility in the swim test. One week of insulin treatment (0.1 IU/g/day) partially antagonized this change. The locomotor activity scores in the streptozotocin-treated mice were lower in the holeboard but higher in the plus maze than in the controls; therefore, the lengthened immobility was not likely to be due to a general motor impairment. No significant changes in the time spent in social interaction or aggressive behavior were found in the streptozotocin-treated mice. The results indicate that streptozotocin-treated mice show lengthened immobility in the swim test.

Aggression↗
PubMed1990

Effect of tryptophan on the behavior of nonstressed and stressed mice in Porsolt's swim test.

The effect of tryptophan on immobility in Porsolt's swim test was studied in male NIH Swiss mice. Preexposure to a swim or fight-stressor was included in the design. Doses of tryptophan (0, 12.5, 50, 75, 100, 125 and 200 mg/kg) were administered intraperitoneally 60 min prior to the swim test. In the nonstressed mice tryptophan had an U-shaped dose-response relationship: immobility in the water was dose-dependently shortened after doses from 0 to 100 mg/kg, whereas after 125 and 200 mg/kg tryptophan the immobility times did not differ from the values obtained after a saline injection. Preexposure to a swim- or fight-stressor did not make mice more sensitive to the effects of tryptophan. Tryptophan (0-300 mg/kg) had no effect on exploratory behavior or locomotor activity in the holeboard, suggesting that sedation was not a factor in the swim test results. The findings suggest that tryptophan has antidepressant -like properties in Porsolt's swim test.

Animals↗
PubMed1989

Behavioral, hormonal and neurochemical characteristics of aggressive alpha-mice.

The present study examined the behavioral, neurochemical and endocrinological characteristics of aggressive, male alpha-mice. These mice inflict severe bite marks on other male mice in their cage, but are not attacked themselves. The characteristics of the alpha-mice were compared with those of submissive mice, and of control mice taken from cages in which no severe fighting was observed. The behavioral tests used were Porsolt's swim test of behavioral 'despair', a plusmaze test of anxiety, a holeboard test of exploration and locomotor activity, and a test of seizure threshold to bicuculline. The alpha-mice were found to be immobile in the swim test for a shorter time than the submissive and control mice, and the submissive mice for a longer time than the controls. In the holeboard, the alpha-mice spent less time making exploratory head-dips than the other mice. Submissive mice had elevated 5-HIAA levels in the hypothalamus, hippocampus and brainstem, and the alpha mice had reduced concentrations of dopamine in the brainstem. There were no significant differences in plasma corticosterone or testosterone concentrations between the groups. These findings indicate that in alpha-mice, a number of behavioral and neurochemical characteristics appear together with the unusually high aggressiveness towards cage-mates.

Aggression↗
PubMed1989

Evidence for adenosine A2 receptor involvement in the hypomobility effects of adenosine analogues in mice.

The hypomobility induced by a series of adenosine analogues was investigated using a holeboard test and their behavioral potencies correlated to their reported adenosine A1 and A2 receptor affinities. All of the adenosine analogues dose dependently inhibited both exploratory behavior (head dipping) and locomotor activity. The rank order of potency 5'-ethylcarboxamido adenosine (NECA) greater than 5'-methylcarboxamido adenosine (MECA) greater than N6-[(R)-1-methyl-2-phenylethyl]adenosine (R-PIA) greater than N6-cyclohexyladenosine (CHA) = N6-cyclopentyladenosine (CPA) greater than N6-[(S)-1-methyl-2-phenylethylladenosine (S-PIA) greater than N6-(2-hydroxyethyl)adenosine (2-OH-ethyl) was observed for inhibiting both activities. The behavioral potency of these adenosine analogues correlates extremely well with their reported A2 receptor affinity (r2 = 0.93, P less than 0.01 and r2 = 0.86, P less than 0.05 for locomotor and head dipping activity respectively), but very poorly with their reported A1 receptor affinity (r2 less than 0.02, P greater than 0.50 for both activities). These results suggest that adenosine A2 receptors, but not A1 receptors, may be involved in the hypomobility induced by adenosine analogues.

Adenosine↗
PubMed1989

Attenuation of hypothermic effects of ethanol by alpha 2-adrenoceptor blockers.

Effects of selective alpha 2-adrenoceptor antagonists, atipamezole and idazoxan, on ethanol-induced hypothermia were investigated in mice. Ethanol significantly reduced (P less than 0.001) core temperature whilst both alpha 2-adrenoceptor antagonists were without effect when administered alone. However, both the 1 and 3 mg/kg doses of atipamezole significantly (P less than 0.05) attenuated the ethanol-induced reduction in body temperature 20 and 40 min after administration. The 3 mg/kg dose of idazoxan (but not the 1 mg/kg dose) also significantly (P less than 0.05) attenuated ethanol's hypothermic effect 20 min after administration but this effect was not statistically significant at 40 min. In a subsequent experiment using lower doses of atipamezole (0.03-1.0 mg/kg) the attenuation of ethanol-induced hypothermia caused by atipamezole was found to be dose-related. The effect of the benzodiazepine inverse agonist Ro 15-4513 on ethanol-induced hypothermia was also investigated. This compound possessed an intrinsic hypothermic action but neither attenuated nor enhanced the hypothermic effect of ethanol. These results suggest that alpha 2-adrenoceptor can, at least partially, modulate the hypothermic effects of ethanol.

Adrenergic alpha-Antagonists↗
PubMed1989

Antagonism of the intoxicating effects of ethanol by the potent benzodiazepine receptor ligand Ro 19-4603.

The effects of the imidazothienodiazepinone Ro 19-4603 were investigated in mice. Ro 19-4603 (0.03-0.3 mg/kg) caused a dose-related reduction in seizure threshold to i.v. bicuculline. Doses of 0.1-3 mg/kg induced seizures in some but not all mice, consistent with its suggested action as a partial benzodiazepine receptor inverse agonist. Ro 19-4603 (0.01-0.3 mg/kg) attenuated the intoxicating effects of ethanol (2.4 g/kg) and was as effective as Ro 15-4513 in this respect.

Animals↗
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

NECA-induced hypomotility in mice: evidence for a predominantly central site of action.

The behavioral effects of four adenosine analogues (NECA, CHA, CPA and CV-1808) were investigated in mice using a holeboard test, which measures both directed exploration (head-dipping) and a locomotor activity. NECA, CHA and CPA showed significant dose-related reductions in all the holeboard measures (NECA much greater than CHA = CPA), whilst CV-1808 showed no significant effect on any of the measures over the dose range tested. In a subsequent experiment NECA-induced hypomotility was attenuated by the adenosine receptor antagonists, theophylline (which is both centrally and peripherally active) and, though to a lesser extent, by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (8-pSPT), which poorly penetrates the blood-brain barrier. The results suggest that NECA-induced hypomotility may be predominantly mediated centrally since the centrally active antagonist was the most effective in reversing the effect, however, peripheral mechanisms may also play a role since equimolar concentrations of 8-pSPT elicit some reversal of NECA-induced hypomotility.

Adenosine↗
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↗
PubMed1988

Conditioned taste aversions produced by nicotine in Roman High and Low Avoidance strains of rats.

Rats of the RHA/iop and RLA/iop strains have been compared in a conditioned taste aversion procedure using nicotine (0.4 mg/kg SC) as the UCS. The procedure utilised a balanced, within-subject design for assessing discriminative aversions to drug- and saline-paired flavoured solutions. Nicotine produced clear aversions in both strains and there were no detectable differences in acquisition. During extinction, rats of the RHA/iop strain consumed more of the drug-paired flavoured solution than rats of the RLA/iop strain, and this difference became greater as the number of extinction trials proceeded. Differences in total fluid intake were too small to account for these effects that were also shown by changes in proportional intake when both flavoured solutions were presented simultaneously. Aversion was, therefore, rather weaker in RHA/iop rats than in RLA/iop rats. These results suggest that rats of the two strains do not differ in "learning ability" in a general way, and support interpretations based on differences in emotionality.

Animals↗
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↗