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Biomedical subjects

M J Durcan

Publications and source records attributed to M J Durcan.

49 records · Page 3Linked to original sources
PubMed1988

Chronic antidepressant drug regimes and food and water intake in rats.

Food and water consumption were measured in rats prior to and during a course of antidepressant drug administration. Desmethylimipramine (DMI, 10 mg/kg/day), clorgyline (1.0 mg/kg/day) or saline were injected IP for 30 days. Food and water intake in the DMI- and clorgyline-treated rats was initially and significantly decreased but progressively returned towards pretreatment levels over the course of the drug administration. The effects of these antidepressant drug treatments on food and water intake appeared to consist of two components: (a) a rapid suppressive effect, possibly associated with an acute central action of these drugs (and perhaps a slight initial stress effect related to the drug administration) and (b) an adaptive effect over the course of the treatment which may involve changes in monoaminergic neurotransmitters or receptor status in those brain regions associated with feeding behavior. The similarities of the results of these treatments and those seen with chronic stress are discussed.

Animals↗
PubMed1988

Circadian studies of 5HT2 receptors: effects of clorgyline administration.

This paper demonstrates the application of an assay design that is particularly valuable for estimating receptor number (Bmax values) and affinity (Kd values) in many small samples of tissue. It is illustrated by its application to a study of possible circadian rhythms in the numbers of 5HT2 receptors in the rat cerebral cortex. The assay design involves the use of only two radioligand concentrations, the lower one being close to Kd (estimated from pilot studies) and the upper one close to 4 times this concentration. The results show that chronic clorgyline (1 mg/kg/day/28 days) administration to rats results in an 18% decrease in the number of cortical 5HT2 receptors (as measured by specific [3H]ketanserin binding). There is no significant circadian rhythm in receptor number in either the control or the MAOI-treated group. There is however, evidence of co-variation between the pairs of control animals housed in the same cage, and interestingly, that this effect is abolished by treatment with the MAOI.

Animals↗
PubMed1988

An examination of experimental design in relation to receptor binding assays.

1. Real and computer-simulated data were used to examine the efficiency of designs for receptor binding assays. 2. Initially, several different concentrations of [3H]-ketanserin were used in receptor binding studies, using membrane preparations from rat cerebral cortex to establish the form of the binding curves and to investigate the relationship between the variance of the binding measurements and their means. 3. The data showed that the specific binding could be modelled by a simple rectangular hyperbola, and were consistent with the assumption that the binding measurements have a constant coefficient of variation (0.1). 4. Computer-simulated data, with a coefficient of variation of 0.1, were then used to look at the precision of estimates of KD and Bmax obtained through the use of assay designs based on replicate incubations at two radioligand concentrations, or through the use of a geometric sequence of 5-7 radioligand concentrations. In each case, the influence of varying amounts (3.8-50%) of non-specific binding at KD on the precision of these estimates was monitored. 5. The results (a) illustrate the problems which arise in the analysis of receptor binding data when there are relatively high amounts of non-specific binding in combination with a constant coefficient of variation, (b) calculate the errors involved and (c) quantitate the relative merits of 2, 5, 6 and 7 point saturation curves in the estimation of Bmax and KD.

Animals↗
PubMed1988

Interactions of 5HT reuptake inhibitors and ethanol in tests of exploration and anxiety.

Treatment with 5HT reuptake inhibitors has been shown to attenuate ethanol consumption in both animals and humans. These experiments investigate in mice the interactions of the 5HT reuptake inhibitors fluoxetine, citalopram and fluvoxamine and the NA uptake inhibitor desipramine with ethanol in the holeboard test and the elevated plusmaze test of anxiety. Ethanol (2.4 g/kg) increased activity both in the holeboard and on the plusmaze, decreased both the number and duration of head-dips in the holeboard, and increased both the percentage time and percentage entries on to the open-arm of the plusmaze (reflecting its anxiolytic properties). On their own, the selective 5HT uptake inhibitors fluoxetine, fluvoxamine, and citalopram and the NA uptake inhibitor desipramine (10-20 mg/kg) did not significantly alter any of the behavioral measures. The only consistent interaction was seen with fluoxetine which reduced ethanol's anxiolytic effects at the 20 mg/kg dose without altering ethanol's effects on exploration or locomotion. The results suggest that the attenuation of ethanol's anxiolytic properties by fluoxetine may not be serotonin related since other 5HT reuptake inhibitors did not show this effect at the doses used.

Animals↗
PubMed1987

Subcellular distribution of beta-adrenoceptors in brain following administration of antidepressant drugs.

The distribution of specific binding of [3H]dihydroalprenolol([3H]DHA) in sucrose gradients (0.2-1.75 M), containing homogenates of the cortex of rat brain, centrifuged to equilibrium (110,000 g/16 hr), was examined in controls and after treatment with antidepressant drugs. There were no significant changes in the specific binding of [3H]DHA after acute administration of desipramine (DMI, 50 mg/kg) or clorgyline (20 mg/kg), either in terms of the number of receptors or distribution in the sucrose gradient. There was a significant decrease (29%) in the number of beta-adrenoceptors after the chronic regimen with DMI, but again no apparent alteration in the density of the receptor-containing membranes, both samples having a maximum distribution at approximately 1.1 M sucrose. Non-specific binding was maximal at 0.65 M sucrose. Electron microscopy showed that the non-specific binding was largely to myelin and the fraction containing most specific binding was composed of membrane fragments. The activity of Na+ K+ ATPase had a single broad peak (maximum at 1.1 M sucrose). Thus, at the times studied, in vivo desensitisation/internalisation of cortical beta-adrenoceptors did not apparently occur following large acute doses of antidepressant drugs and furthermore the down-regulation which followed the chronic regimen with DMI did not involve migration of receptors into "light density fractions" which are reported to be present after acute exposure to agonists in vitro.

Animals↗
PubMed1985

Clonidine induced sedation is not altered by repeated stress in the RHA/iop and RLA/iop strains of rats.

An hypothesis that repeated stress results in central changes in alpha 2-adrenoceptor sensitivity was investigated using a behavioural test. Stressed (immobilisation for 2 h/day for 7 days) and unstressed rats from the RHA/iop and RLA/iop strains were tested for the sedative effects of the alpha 2-adrenoceptor agonist clonidine on Y-maze behaviour. The measures used were number of lines crossed, arm entries and rearing. The stressed animals showed higher scores for line crossings and rearing; but the only significant difference between the strains was for rearing, which was higher for RHA/iop. Clonidine significantly depressed all the measures of activity. However, there was no evidence of an interaction of the drug with stress for any of the measures. It is concluded that neither repeated stress nor genetic differences in the ability to cope with stress influence the behavioural effects of clonidine. This suggests that stress responses are not related to the central alpha 2-adrenoceptor system.

Animals↗
PubMed1985

Chronic clorgyline and pargyline increase apomorphine-induced stereotypy in the rat.

The effects of monoamine oxidase inhibiting antidepressant drugs on behavioral and biochemical measures of dopamine receptor status were measured in the rat. Male Wistar rats received clorgyline (1 mg/kg/day for 21-28 days), pargyline (1 mg/kg/day for 21-28 days) or a combination of these regimens. They were then either tested for stereotypy induced by 1 mg/kg SC injection of apomorphine or were sacrificed and their striata used to measure specific [3H]spiroperidol binding. All three chronic treatment regimens produced statistically significant increases in apomorphine induced stereotypy: there was, however, no significant difference between the three drug regimens. None of the antidepressant drug treatments significantly affected [3H]spiroperidol binding in the corpus striatum. This study demonstrates that behavioral and biochemical measures of dopamine function may not always be closely correlated. It is proposed that the behavioral changes may be related to alterations in other monoaminergic systems, which are known to have fibres running into the nigrostriatal pathway.

Animals↗
PubMed1984

Differences in the stereotypy response but not the hypomotility response to apomorphine in the Roman High and Low avoiding strains of rats.

Two experiments were carried out to investigate differences in the behavioural responses to "high" and "low" doses of apomorphine in two strains of rats selectively bred for high and low avoidance on a two-way active avoidance task: the Roman High and Low Avoiders. Significant strain differences were found in the stereotypy resulting from a high dose of apomorphine (2 mg/kg s.c.). In a second experiment no strain differences were, however, apparent for the hypomotility produced by low doses of the drug (0.05 mg/kg s.c.). Pretreatment with a low dose of apomorphine had no effect on the stereotypy response when the animals were subsequently retested with the high dose. These results may indicate differential sensitivities of dopamine receptors in these strains.

Analysis of Variance↗
PubMed1984

Apomorphine-induced stereotypy: function of age and rearing environment.

Rats of different age groups ("young" vs. "old"), reared in isolation and social groups were tested for differences in apomorphine-induced stereotypy. Sensitivity to apomorphine (2 mg/kg SC) was found to be a function of an interaction between rearing environment and age. The "younger" isolated animals displayed greater stereotypy than group-reared and "older" isolated animals. Rearing environment and age, as main factors, did not have significant influence on drug-induced stereotypy.

Aging↗
PubMed1983

Alpha-adrenoceptor number and function in rat cortex after ethanol and immobilization stress.

Alpha-Adrenoceptor number and function were assessed in rat cortex after ethanol and immobilization stress. Rats subjected to immobilization stress for 2 h/day/7 days showed a significant reduction in alpha 2-adrenoceptors in cortex ( [3H]clonidine binding) but no change in alpha 1-adrenoceptors ( [3H]prazosin binding). The inhibitory effect of clonidine (500 nM) on 3H efflux from cortical slices preincubated with [3H]norepinephrine was reversed in the stressed animals. These effects on alpha 2-adrenoceptor number and function were reduced when stress was accompanied by chronic administration of ethanol (35% of calories in a liquid diet) although when given alone ethanol produced small changes in the same direction as those produced by stress. It is suggested that, in its effects on cortical alpha-adrenoceptors, chronic ethanol administration attenuates the effects of severe stress though itself perhaps acting as a mild stressor when given as part of a liquid diet regimen.

Animals↗
PubMedDate not supplied

Attenuation of the effects of ethanol on social behavior by alpha 2-adrenoceptor antagonists.

In a social behavior test in mice ethanol (2 g/kg) significantly reduces the time spent in social interaction and increases locomotor activity. The relatively selective alpha 2-adrenoceptor antagonists atipamezole and idazoxan alone have no significant effect on either social interaction or locomotor activity in this test. However, when coadministered with 2 g/kg ethanol, atipamezole (0.3-3.0 mg/kg) significantly attenuated the ethanol-induced reduction in the time spent in social interaction without any effect on ethanol's locomotor stimulant action. Idazoxan (0.3-1.0 mg/kg) also showed a trend towards reversing the reduction in the time spent in social interaction although this was accompanied by a significant attenuation of the locomotor stimulant effect of ethanol. The results indicate that alpha 2-adrenoceptors may modulate ethanol's effects on social interaction in mice.

Adrenergic alpha-Antagonists↗