Chronic emotional stress exposure increases infarct size in rats: the role of oxidative and nitrosative damage in response to sympathetic hyperactivity.

We investigated the level of sympathetic hyperactivity in response to stress exposure in an acute myocardial infarction (AMI) model and the contribution of oxidative and nitrosative damage to this phenomenon. Stress was induced by 20-day administration of different emotional stress factors: daylight/darkness exposure, overcrowding, isolation, new hierarchy, tilting the cage and restriction of water or food. AMI was induced surgically. Heart rate (HR) and heart rate variability (HRV) measurements were done before and after AMI. Oxidant parameters were measured in heart tissue and cortisol levels were measured in plasma specimens. Compared with the nonstressed group, stress-exposed rats showed sympathetic hyperactivity characterized by increased HR together with decreased HRV. In the stressed group serum corticosterone levels were high both before and after AMI. Mean infarct size in the stressed group was significantly larger (44.6+/-3.23% and 53.1+/-4.52%, respectively; P<0.05). Increased tissue malondialdehyde (MDA) levels (0.63+/-0.59 and 1.60+/-0.31 nmol/mg protein, respectively; P<0.05) and decreased superoxide dismutase (SOD) activity and glutathione (GSH) content were seen in stress-exposed rats. Likewise, heart peroxynitrite levels were also high in stress-exposed rats (141.8+/-18 nmol/g tissue vs. 164.2+/-21 nmol/g tissue). Chronic emotional stress is a deteriorating factor for the induction and prognosis of MI. Exaggerated sympathetic activity may be the major contributing factor. Oxidative and nitrosative damage in response to this sympathetic hyperactivity is the key mechanism.

Antidepressant-like effect of hyperbaric oxygen treatment in forced-swimming test in rats.

The present study was undertaken to assess the antidepressant-like activity of hyperbaric oxygen (HBO) treatment and also to investigate whether in the forced-swimming test HBO treatment interacts with the antidepressant effects of fluoxetine, a selective serotonin reuptake inhibitor, and imipramine, which is mainly a noradrenaline reuptake inhibitor. HBO treatment (at 2.4 atmospheres absolute [ATA] for 60 min) significantly reduced the immobility time in this test; in other words, it displayed antidepressant-like activity. The coadministration of HBO with fluoxetine (5 mg/kg) or imipramine (5 mg/kg) at their ineffective doses produced greater inhibition of immobility time compared with HBO alone. In conclusion, HBO treatment might be an alternative approach to antidepressant therapy, alone or in combination with antidepressant drugs.

Effect of morphine on the brain histamine levels in stress-exposed rats.

The effect of morphine on brain histamine levels in stress-exposed rats was investigated. It seemed that the brain histamine level was not directly affected by stressors. However, morphine induced a sharp rise in the brain histamine levels in both morphine-treated and morphine-treated stressed groups. This effect of morphine was reversed by naloxone.

The effect of long-term concurrent administration of chlorpromazine and lithium on the striatal and frontal cortical dopamine metabolism in rats.

The effects of lithium and chlorpromazine chronically administered alone and together on the dopamine metabolism in the rat striatum and frontal cortex were investigated by measurement of the levels of dopamine (DA) and its main metabolite, homovanillic acid (HVA). Long-term chlorpromazine administration caused a significant increase in the striatal DA level and a decrease in that of HVA and HVA/DA ratio without any changes in those of the frontal cortex. The prolonged administration of lithium elevated the striatal levels of both HVA and DA, but no change in the frontal cortex was observed. The concurrent administration of chlorpromazine and lithium caused a significant increase in the frontal cortical DA level and a decrease in that of HVA and HVA/DA ratio. The striatal DA and HVA levels increased under the effect of the combined treatment, while the HVA/DA ratio remained unchanged.

Lithium-induced changes in the brain levels of free amino acids in stress-exposed rats.

The effects of stress and lithium on brain free amino acid levels in rats were investigated. Stress caused a significant decrease in the brain levels of alanine, ammonia, arginine, isoleucine, lysine and phenylalanine. Lithium by itself induced a significant increase in the brain levels of arginine and threonine, and a significant decrease in those of alanine, ammonia, aspartic acid, glutamic acid, glycine, lysine, phenylalanine and tyrosine. Lithium and stress together significantly decreased brain levels of alanine, arginine, aspartic acid, glycine, isoleucine, leucine, lysine, phenylalanine and tyrosine, and significantly increased that of serine.

The antagonizing effect of aspartic acid on morphine withdrawal and levallorphan-precipitated abstinence syndrome signs and on associated changes in brain levels of free amino acids in the rat.

We have previously demonstrated the antagonizing effect of aspartic acid on some effects of morphine and on the development of physical dependence on, and tolerance to, morphine. In the present study, we have withdrawal from morphine or administration of a morphine antagonist. For this purpose sixty five white rats were given morphine and aspartic acid separately and in combination in a 5% saccharose solution instead of drinking water for 30 days. Some of the dependent rats were then withdrawn and others were injected with levallorphan. Flying, jumping, wet-dog shaking, body weight loss and motor activity were estimated and free amino acid levels in the brain were determined. Aspartic acid was found to prevent or antagonize the behavioural signs and the changes in the free amino acid levels in the brain. The results are discussed in the light of the previous data.

The antagonizing effect of aspartic acid on the brain levels of monoamines and free amino acids during the development of tolerance to the physical dependence on morphine.

Since it has been shown in previous study that aspartic acid prevents the development of physical dependence on and tolerance to morphine and antagonizes the abstinence syndrom signs, the biochemical bases of that prevention were investigated in the present study. The brain contents of serotonin, DA, NA, and free amino acids of the rats given aspartic acid and morphine separately and in combination were determined. It has been observed that most of the morphine-induced changes in the brain were normalized in the group given aspartic acid and morphine together. The relative ineffectiveness of aspartic acid in normalizing some amino acid levels decreased by morphine was discussed and some logical explanations were found.

Hyperbaric oxygen treatment reduces carrageenan-induced acute inflammation in rats.

The present study was designed to assess the anti-inflammatory activity of hyperbaric oxygen treatment by comparing it with that of diclofenac, a nonsteroidal anti-inflammatory drug, and also to investigate whether hyperbaric oxygen treatment enhances the anti-inflammatory effect of diclofenac in carrageenan-induced paw edema which is commonly employed as an acute inflammation model in rats. Hyperbaric oxygen treatment and diclofenac (20 mg/kg) markedly reduced the carrageenan-induced paw edema in rats. In other words, they displayed anti-inflammatory activity. On the other hand, hyperbaric oxygen treatment did not consistently modify the anti-inflammatory effect of diclofenac in this model.

Nifedipine alters serum theophylline levels in asthmatic patients with hypertension.

The effect of nifedipine on serum theophylline levels in 13 female hypertensive patients having asthma on theophylline therapy has been investigated. Administration of a slow release theophylline product in a dose of 200 mg bidaily for 15 days provided a steady-state through serum theophylline concentration (11.2 +/- 2.7 micrograms/ml). After this period, 10 mg bidaily nifedipine was added to therapy and trough serum theophylline levels, pulmonary function tests and blood pressure measurements have been performed following 15 and 45 days of simultaneous use of theophylline and nifedipine. No change has been observed in serum theophylline level after 15 days of simultaneous use, however after 45 days, serum theophylline level was significantly lower (7.3 +/- 1 micrograms/ml). There were no changes in clinical responsiveness of either of these drugs.

The effect of ofloxacin and ciprofloxacin on pentylenetetrazol-induced convulsions in mice.

There have been several reports that convulsions, although rare, occur in patients who received fluoroquinolones. In this study, conducted for the evaluation of the convulsant action of fluoroquinolones, the effect of ofloxacin and ciprofloxacin on pentylenetetrazol-induced convulsions were investigated in mice. Mice were pretreated intraperitoneally (IP) with saline, ofloxacin (20 or 80 mg/kg) or ciprofloxacin (20 or 80 mg/kg) 30 minutes before subcutaneous (SC) administration of pentylenetetrazol (40 or 60 mg/kg). In another experiment, diazepam (5 mg/kg) was injected (IP) in mice alone or in combination with ofloxacin (80 mg/kg) 30 minutes before pentylenetetrazol (40 mg/kg) administration (SC). In each experiment mice were observed over the following hour for the incidence and onset of clonic convulsions. Results showed that both doses of ofloxacin increased the incidence of clonic convulsions induced by 40 mg/kg pentylenetetrazol. This effect, however was only significant in the higher dose and inhibited by diazepam. On the other hand, a similar proconvulsant effect by ciprofloxacin could not be demonstrated.

Bay K 8644 potentiates the anxiolytic effect of ethanol.

The possible role of voltage-sensitive calcium channels (VSCCs) in the anxiolytic effect of ethanol was investigated using three different doses of ethanol (0.5, 1.0 and 2.0 g/kg) with calcium agonist Bay K 8644 (0.5 mg/kg) and calcium antagonist nifedipine (5 mg/kg) in rats. Ethanol produced an anxiolytic effect in a dose-dependent manner. The Bay K 8644-potentiated anxiolytic effect of ethanol, however, Bay K 8644 did not alter anxiety when used alone. Nifedipine itself showed an anxiolytic effect but did not change the ethanol-induced anxiolytic effect. This finding may lead to the consideration of the neurochemical mechanisms of the anxiolytic effects of ethanol and nifedipine as they vary from each other.

The effect of ofloxacin on pentobarbital-induced sleep in mice.

There have been several reports that insomnia occurs in some patients who receive ofloxacin. Since almost no experimental data on ofloxacin-induced insomnia were available, this study was conducted for the evaluation of ofloxacin effects on sleep parameters in mice. In Experiment 1, mice were pretreated with ofloxacin (20 or 40 mg/kg IP) or saline 15 minutes before sodium pentobarbital (35 mg/kg IP). Experiment 2 was carried out in two days. On the first day mice were treated twice, in the morning and in the evening, with ofloxacin (20 or 80 mg/kg IP) or saline. On the second morning, mice were pretreated with the same doses of ofloxacin or saline 15 minutes before sodium pentobarbital (35 mg/kg IP). Sleep latency and sleeping time were recorded in each experiment. Results showed that ofloxacin had no apparent effect on sleep latency, but caused a shortening in sleeping time. However, this effect was significant only in the 40 and 80 mg/kg ofloxacin-treated groups.

The inhibitory effect of liposome-encapsulated indomethacin on inflammation and platelet aggregation.

A comparison has been made between liposome-encapsulated and free indomethacin for their anti-inflammatory activities in the carrageenan paw oedema test in rats, and their inhibitory effect on platelet aggregation induced by adenosine 5-diphosphate (ADP) in-vitro. Free indomethacin, 3 mg kg-1, strongly inhibited carrageenan-induced oedema and a similar inhibitory activity was shown by 0.3 mg kg-1 of encapsulated drug. For the inhibition of platelet aggregation, the threshold concentration of free drug was 0.559 mM. At this concentration, at least 5 min incubation was needed to achieve 12.5% and 45 min for 50% inhibition. The inhibition was much stronger with encapsulated drug, and pre-incubation of 28 microM encapsulated drug for 10 min with platelet-rich plasma before addition of ADP completely inhibited platelet aggregation.

Effects of opioid-type stressors on serum digoxin-like immunoreactivity in rats.

The effects of opioid-type stressors (immobilization, electric footshock and forced swimming) on serum digoxin-like immunoreactivity (SDLI) were investigated in rats. All of the stressors significantly elevated the SDLI. Naloxone treatment after application of stressors prevented the elevation of SDLI, whereas naloxone treatment alone did not cause any significant changes. The observed increase in SDLI in this study may be attributed to the actions of endogenous opioid peptides released during stress.

Protective role of immobilization on ouabain-induced arrhythmias.

The effects of the opioid-type stressor, immobilization, on severity of ouabain-induced cardiac arrhythmias and the possible involvement of serum catecholamines were investigated in rats. Immobilization significantly reduced the number of ventricular premature beats and the incidence of ventricular tachycardia episodes. The arterial serum catecholamine levels (A, NA and DA), measured immediately after the stressor application, were increased significantly and were in negative correlation with the arrhythmia parameters. Both changes were reversed by naloxone (5 mg/kg) treatment after application of immobilization. The effects observed in this study may be attributed to the actions of endogenous opioid peptides released during stress.