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Biomedical subjects

W H Vogel

Publications and source records attributed to W H Vogel.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of acute and chronic diazepam treatment on stress-induced changes in cortical dopamine in the rat.

The mesocortical dopamine system is thought to play an important role in the etiology of the stress response. Dopamine (DA) has been shown to accumulate in the rat frontal cortex in response to a wide variety of stressors. Diazepam, an anxiolytic benzodiazepine, can reverse the effects of stress on cortical DA. We investigated the effects of acute and chronic diazepam administration on immobilization stress-induced changes of the DA system in the frontal cortex of the rat. In the first study, 2.5 mg/kg diazepam was administered 20 min prior to 40 min of immobilization stress. Acute diazepam significantly reduced basal levels of extracellular DA and antagonized the stress-induced increase in cortical DA when compared to untreated stressed rats. Acute diazepam did not significantly effect extracellular DOPAC. In the second study, an experimental group of rats was given approximately 2 mg/kg/day diazepam in their drinking water for 3 weeks. This treatment significantly reduced anxiety as assessed by a staircase test for anxiety. Chronic diazepam had no effect on basal levels of cortical DA. However, chronic diazepam treatment also attenuated stress-induced increases in extracellular DA when compared to untreated stressed control rats. Chronic diazepam did not affect stress-induced changes in DOPAC but it did antagonize the effects of stress on HVA. Thus, acute and chronic diazepam treatment can antagonize stress-induced activation of the mesocortical DA system. It is proposed that this effect is produced through an enhancement of GABAergic neurotransmission by diazepam. The role of the dopaminergic system during stress, anxiety, and schizophrenia is discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Effects of selective serotonergic agonists on aggressive behavior in rats.

The effects of the relatively specific serotonergic agonists 8-OH-DPAT (5-HT1A), TFMPP (5-HT1B), and DOB (5-HT2) were studied on defensive aggressive behavior in rats using the water competition test, 8-OH-DPAT (up to 0.25 mg/kg) and TFMPP (up to 1 mg/kg) were found to be ineffective, whereas DOB (up to 0.4 mg/kg) significantly reduced aggressive behavior in this test as well as in the offensive aggression test of the resident-intruder model. These results, combined with those from other studies, suggest that stimulation of 5-HT1A, 5-HT1B, and 5-HT2 receptors reduces offensive aggression, whereas defensive aggression is only decreased by 5-HT2 stimulation.

Aggression↗
PubMed1994

Impact of stress and triiodothyronine on plasma magnesium fractions.

The differential regulation of free and bound plasma magnesium was studied in healthy volunteers exposed to various forms of stress, and patients screened for thyroid disorder. Both ergometric (7 min) and psychological (45 min) stress had no effect on free plasma magnesium, but increased the bound fraction. Before combined physical and psychological stress (45 min aerobatics) there was no correlation between the plasma fractions of magnesium; thereafter, there was a strong negative correlation between increased free and decreased bound magnesium. Three days of training in ground combat increased significantly the plasma levels of both magnesium fractions. Patients screened for thyroid disorder had a significant, positive correlation between both plasma fractions of magnesium, and a highly significant negative correlation between plasma T3 and the two magnesium fractions. No clear correlation between plasma catecholamines and magnesium levels was seen under any of the above conditions. Overall, the data show that the evaluation of the functions of circulating magnesium requires the specific measurement of the free and bound fractions.

Austria↗
PubMed1994

Quantitative trait loci mapping of three loci controlling morphine preference using inbred mouse strains.

Quantitative trait loci mapping was used to identify the chromosomal location of genes which contribute to oral morphine preference (in a two-bottle choice paradigm) of C57BL/6J mice, compared to DBA/2J mice. An F2 intercross of these two strains (606 mice) was phenotyped for morphine preference and those mice demonstrating extreme values for morphine consumption (the highest and lowest 7.7%) were genotyped for 157 murine microsatellite polymorphisms. Maximum likelihood methods revealed three loci on murine chromosomes 1, 6 and 10 which are responsible for nearly 85% of the genetic variance observed between the two parental strains.

Animals↗
PubMed1994

A study of oral morphine preference in inbred mouse strains.

C57BL/6J mice, in two-bottle choice paradigms, show increased oral morphine consumption, compared with DBA/2J mice. To determine whether this C57 morphine preference reflects differences in the receptor-mediated, reward-based action of morphine (as opposed to pharmacokinetic or gustatory differences), three experiments were performed. Consistent with previous two-bottle choice experiments, C57 mean (+/- S.D.) morphine consumption was 18 +/- 3 mg/kg/day, while the DBA mice consumed 1.4 +/- 1.2 mg/kg/day. Intraperitoneal naltrexone produced a 50% decrease in C57 morphine consumption (p < 0.01), while DBA mice showed no change. Consumption of fluid from the control bottle was not changed for either strain. Fifteen and 30 min after oral consumption of a morphine solution, plasma levels of morphine and its glucuronide derivative were not different between these two strains. C57 mice maintained a daily morphine intake of approximately 20 mg/kg across morphine concentrations of 0.05-0.4 mg/ml. These experiments suggest that the difference in oral morphine preference between C57 and DBA mice represents a reward-based mechanism which is mediated through opiate receptors.

Animals↗
PubMed1994

Maudsley reactive and non-reactive rats differ in exploratory behavior but not in learning.

The Maudsley reactive (MR) and Maudsley non-reactive (MNR) inbred rat strains were created as an animal model of anxiety, based on open field behavior. We wished to determine whether previously described characteristic open field behavior and learning deficits in conditioned avoidance could be generalized to other paradigms of exploratory behavior (such as the staircase test) and learning (such as the T-maze swim test). As with other open field paradigms, the MR rats showed stable and large differences in the staircase test, compared with the MNR rats. In contrast, large and stable learning differences in conditioned avoidance and T-maze swim tests were not observed. We conclude that the MR rats exhibit exploratory behavior that is inhibited in a wide variety of paradigms, but learning deficits are not major characteristics of the phenotype. The inhibited exploratory behavior is a stable characteristic with large inter-strain differences, making measures of open field behavior suitable for quantitative trait loci analysis to determine the genes which explain these large and stable strain differences. Identification of these genes could provide clues to the genetic origins of some human anxiety disorders.

Animals↗
PubMed1993

Aging and temporal discrimination of brief auditory intervals.

In a duration-discrimination experiment, young adults (mean age = 25.1), middle-aged adults (mean age = 45.5), and older adults (mean age = 64.6) were presented with two very brief auditorily marked intervals per trial, and their task was to decide which of the two was longer in duration. An adaptive psychophysical procedure was used to determine difference thresholds in relation to a constant standard interval of 50 ms. It was found that duration-discrimination performance was unaffected by age; all three age groups yielded a difference threshold of approximately 17 ms. It was concluded that the ability to discriminate durations of very brief auditory intervals appears to be based on an underlying timing mechanism that does not slow down with advancing adult age.

Adult↗
PubMed1993

Detection and evaluation of persisting stress-induced hormonal disturbances by a post stress provocation test in humans.

Eighteen healthy army officers were subjected after prolonged rest to exhaustive ergometric work for about 15 minutes. Before and afterwards blood was taken from the cannulated antecubital vein for determination of free and sulfoconjugated catecholamines, cortisol, glucose, and white blood cell count. One week later, the same procedure was repeated with the same subjects with the difference that the probands underwent about 2.5 hours of difficult mountain climbing and a subsequent rest of 1.5 hours before ergometry. The most important results were: 1) total and bound fractions of catecholamines showed some significant differences between the first and second ergometry due to the previous mountain climbing stress; 2) serum cortisol did not increase after the first ergometry but did so significantly after the second ergometry due to the previous stress; low cortisol is not always indicative of the absence of stress; 3) the absolute number of white blood cells increased in both situations, correlated significantly with the severity of the stress and the individual increases were more person than situation specific and; 4) blood glucose remained unaffected in both situations. We conclude that a previous stress experience can affect a second stress response and that such a post stress provocation test can uncover persistent hormonal alterations. This procedure may be useful for the evaluation of inaccessible stress situations from subsequent stress measures.

Adult↗
PubMed1993

Effects of repeated stress on plasma arginine levels in young and old rats.

The effect of age and recurring stress responses on endogenous plasma arginine (ARG) concentrations were determined. Blood from catheterized young (3 months) and old (24 months) were used to ascertain the plasma concentrations of ARG under baseline conditions, during a 30-min immobilization experience and during a 3.5 h poststress period. Rats were again immobilized and blood drawn following a 1 day rest period (day 3) and then after an additional 3 day rest period (day 7). For young animals, ARG levels decrease significantly after 30 min of stress and remain suppressed during the entire poststress period (3.5 h). After a 1 day rest period, these young rats may have exhibited adaptation to stress on day 3. Old animals showed little or no reduction in plasma ARG concentrations during and after immobilization stress exposure on all three occasions. Baseline levels of old animals were lower in comparison to young animals and their stress responses were smaller. Thus, it is possible that significant changes in plasma ARG levels (as the nitric oxide precursor) during or after stress could serve as an indicator of impending pathology such as cardiovascular disease or immunocompetency.

Adaptation, Psychological↗
PubMed1993

Modulation of the stress response by ethanol in the rat frontal cortex.

Microdialysis was used to characterize the effects of two doses of ethanol, stress, and their interaction on the dopaminergic system. Saline-treated animals showed no changes in levels of dopamine (DA) or dihydroxyphenylacetic acid (DOPAC). Neither a 0.5- nor a 2-g/kg IP injection of ethanol had an effect on DA or DOPAC in resting animals. Immobilization caused marked increases in DA levels and smaller increases in DOPAC. Pretreatment with 0.5 g/kg ethanol did not reduce the stress-induced increase in DA or DOPAC. However, pretreatment with 2 g/kg ethanol strongly reduced and antagonized the stress-induced increases in DA and potentiated the stress-induced increase in extracellular DOPAC. Our data show that ethanol can have different, dose-dependent effects in resting vs. stressed animals, that it has different effects on DA and DOPAC, and that the high dose antagonized stress-induced increases in DA. The latter adds biochemical evidence to the tension-reduction hypothesis of ethanol by perhaps implicating a reduction in the DA stress response by ethanol as a contributing factor in the development of alcoholism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Relevance of "irrelevant" facts in medical education: the value of basic science teaching for later medical practice.

The relationship between performance measures in medical school and in practice is addressed in this article in terms of the relevance to the physician's practice of the facts learned in medical school. It is argued that despite the fact that "relevance" and "irrelevance" are relative terms, medical education should place emphasis on the "core" curriculum on the assumption that core materials have important applications in practice and therefore are more relevant when investigating relationships between performances in medical school and after graduation. Although some of the "relevant" facts may seem "irrelevant" to medical students, medical school faculty and members of curriculum committees should be committed to include relevant facts in the core curriculum based on their professional hindsight and feedback from practicing physicians.

Clinical Competence↗
PubMed1992

Effects of adinazolam on plasma catecholamine, heart rate and blood pressure responses in stressed and non-stressed rats.

Adinazolam (ADI) is a new benzodiazepine with anxiolytic and antidepressant properties. To assess its effects on the acute stress response, rats were given a single intraperitoneal injection of 2.5 or 5.0 mg/kg of ADI and stressed for 1 hr by restraint. Neither dose of ADI had any effect on heart rate, blood pressure or norepinephrine (NE) and epinephrine (EP) in plasma in the resting rats. In the stressed animal, 2.5 and 5.0 mg/kg of ADI did not affect stress-induced increases in heart rate or blood pressure but both significantly reduced the stress-induced increases in plasma NE and EP. During certain stressful experiences in patients with abnormally-increased sympathetic drive, ADI may be therapeutically useful in reducing high levels of catecholamines.

Animals↗
PubMed1992

Pharmacologic properties of the internal clock underlying time perception in humans.

Performance on temporal discrimination of time intervals in the range of milliseconds is interpreted by the assumption of an internal clock; the higher the clock rate the better the temporal resolution of the internal clock will be, which is equivalent to more accuracy in timing of brief intervals. Although there is some evidence from animal and human studies suggesting that the clock rate depends on the effective level of brain dopamine (DA), the findings are not conclusive. Therefore, an alternative interpretation of the pharmacologic properties of the internal clock has been introduced. According to this interpretation, the internal timing mechanism can be seen as a biological rhythm that is susceptible to chronomutagenic agents, i.e., pharmacologic compounds that are able to produce an alteration in the period of a biological rhythm. To elucidate the pharmacologic properties of the internal timing mechanism, in a double-blind study either 1750 mg of the DA antagonist alpha-methyl-p-tyrosine (AMPT), 0.65 g/kg ethanol which possesses chronomutagenic effects, or placebo were applied to 80 male subjects. As measures of performance, difference threshold estimates in relation to a 50- and a 1,000-ms standard interval and respective response latencies were computed. Furthermore, urinary levels of DA, DOPAC, and HVA were quantified by HPLC analysis. Although AMPT treatment resulted in a pronounced reduction of more than 50% for DA, DOPAC, and HVA, temporal discrimination was not affected. On the other hand, ethanol induced a significant impairment in performance on temporal discrimination in the range of milliseconds as compared to placebo. Neither temporal discrimination in the range of seconds nor response latencies were affected by the drugs applied in this experiment. Our findings suggest that the internal timing mechanism underlying temporal discrimination of intervals in the range of milliseconds is independent of the effective level of brain DA. More likely, pharmacologically induced changes in clock rate appear to depend on the chronomutagenic effects of the drug applied. Furthermore, the absence of ethanol-induced changes in performance on temporal discrimination of longer intervals in the range of seconds supports the assumption of two distinct timing mechanisms underlying temporal discrimination in the millisecond and second range.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

In vivo microdialysis study of brain ethanol concentrations in rats following oral self-administration.

Using intracerebral microdialysis, the time-course of ethanol absorption was determined in the striatum of rats after oral self-administration of an ethanol solution. Microdialysis samples were collected every 10 min for 1 hr before and 1 hr after consumption of ethanol over a 5-min period. Substantial levels of ethanol were detected in the brain in the first sample taken after self-administration although these levels did not correlate with the amount of ethanol consumed. Striatal ethanol levels reached maximum or near maximum by the second sample and remained constant for the time points between 20 and 60 min; at these times, brain ethanol levels correlated significantly with the amount consumed. This study demonstrates that oral consumption of ethanol leads to measurable brain levels within a relatively short time. Results suggest that experimental animals may experience the central effects of ethanol during the course of drinking and this could play a role in alcohol preference or avoidance behavior.

Alcohol Drinking↗
PubMed1990

Voluntary alcohol and cocaine consumption in "low" and "high" stress plasma catecholamine responding rats.

Alcohol (ethanol) and cocaine preference in a free-choice, two-bottle situation was measured in two groups of male and female "low" and "high" plasma catecholamine stress responding rats. Alcohol intake of a 5% solution (percent or mg/kg) showed markedly different but individually consistent intake among animals. "High" plasma catecholamine stress responders consumed more ethanol than did "low" responders. A similar finding was made when animals consumed a 10% solution; fluid intake fell but total ethanol intake remained the same. "High" responders drank more than did "low" responders. After a period of 4 weeks of water only, animals were reexposed to 5% ethanol and a significant positive correlation was seen in the drinking habits of the animals. Afterwards, exposure to a 0.02% cocaine solution resulted in cocaine intake which varied among animals, but was consistent for an individual rat and did not correlate with alcohol consumption. In general, ethanol and cocaine consumption correlated positively with the plasma catecholamine stress response. No significant differences in drinking habits were observed between the sexes. Thus, alcohol preference is a relatively stable characteristic of an animal, is higher in "high" as compared to "low" plasma catecholamine stress responders and does not correlate with voluntary cocaine consumption.

Alcohol Drinking↗
PubMed1990

The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels.

Advanced emphysema with bronchitis is associated with significant weight loss and malnutrition, the true cause of which has not been clearly identified. The purpose of this exploratory study was to compare plasma amino acids and related compounds and catecholamines in a group of patients with advanced end-stage emphysema with a control group of similar age and sex in an effort to further understand this malnourished state. Fasting blood samples were obtained by venipuncture after a rest period. Plasma amino acid levels were determined by ion exchange high pressure liquid chromatography with fluorometric detection. Plasma catecholamines were determined by radioenzymatic analysis. Anthropometric measurements, the usually accepted biochemical markers of nutrition, dietary analysis, pulmonary function tests, and a historical analysis of the state of health including drug use and smoking history in each subject were analyzed. Ages and heights were comparable, whereas weights were significantly decreased in the patients with emphysema. Total serum protein and serum albumin values were significantly lower in the patient group. Significant respiratory muscle weakness was indicated by reduced negative inspiratory force in these end-stage patients, contrasting with well-preserved muscle strength usually found in obstructive lung disease. The dietary caloric intake of the patients was comparable to that of the control subjects. We conclude that the fine balance of the amino acid pool in patients with bronchitis and emphysema is well preserved, except for significant elevations of aspartic acid, glutamine, and cystine, and a decreased level of leucine. In addition, norepinephrine levels were significantly increased. Weight loss in patients with emphysema and bronchitis is likely due to increased energy demands related to hypermetabolism.

Aged↗