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Biomedical subjects

W H Vogel

Publications and source records attributed to W H Vogel.

At least 19 recordsLinked to original sources

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

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

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

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

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

The effect of ethanol on stress-induced tachycardia.

A study was designed to answer the questions if low doses of ethanol would reduce stress induced increases in heart rates, if covariations would be observed between ethanol induced changes in heart rates and changes in emotional states and mental performance and if tolerance to ethanol or other personality factors would influence the ethanol induced cardiac effects. Forty-four male students with a history of high and low alcohol consumption according to questionnaire scores were matched for extraversion and neuroticism and then assigned to a group receiving either 0.8 g/kg of ethanol or a placebo drink. A stress condition of mental arithmetic was applied prior to and 45 minutes after ingestion of the drink. Heart rates and ratings of emotional states by adjective check lists were recorded before and after each stress session. A significant reduction of stress induced heart rate increases in both high and low drinking groups but no ethanol dependent change of resting heart rates were observed. Reductions of autonomic stress response by ethanol were weakly but positively correlated to respective reductions of affective stress responses and impairment of the quality of mental performance. High trait anxiety subjects seemed to benefit more from ethanol with respect to reductions of cardiac and emotional arousal than low anxious subjects.

Adult

Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial.

Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population.

Adolescent

The effects of immobilization stress on serum triglycerides, nonesterified fatty acids, and total cholesterol in male rats after dietary modifications.

The effects of acute immobilization stress on triglycerides, nonesterified fatty acids (NEFA) and total cholesterol were determined in serum samples obtained by indwelling jugular catheters from male Sprague-Dawley rats. Stress was evaluated in three groups of rats: (1) those maintained on a regular Purina Chow diet and then fasted for 24 hours; (2) those maintained on this same diet but not fasted (nonfasted) before experimentation; and (3) those maintained on a Purina Chow diet supplemented with cholesterol (1%) and fat (10%) for 6 weeks and nonfasted prior to experimentation. Samples were taken by catheter in the home cage prior to, four times during a one hour stress/nonstress period and thirty minutes after being returned to the home cage for recovery. Nonstressed rats remained in the home cage during the entire 90 minute period. In each dietary state studied, stress affected serum triglycerides and NEFA but not total cholesterol levels. Triglyceride levels in fasted rats increased during the stress period. On the other hand, triglycerides decreased in response to stress in nonfasted rats. In stressed, nonfasted high cholesterol-fed animals, triglycerides were elevated in comparison to their nonstressed counterparts. In both fasted, regular diet-fed and nonfasted, cholesterol-fed rats, NEFA sharply declined from baseline after 5 minutes of stress; NEFA did however increase after fifteen minutes. NEFA levels in both stressed and nonstressed, nonfasted rats also rapidly decreased from baseline and never recovered throughout the session. Total cholesterol did not change in response to stress or dietary modifications. The rats maintained on a high cholesterol diet showed only a diet-induced increase in total cholesterol. Thus, acute immobilization stress affected serum triglyceride and NEFA values and these effects were diet- and time-dependent. Total cholesterol levels were unaffected by stress.

Animals

The plasma catecholamine stress response is characteristic for a given animal over a one-year period.

The same male and female rats with indwelling jugular catheters were stressed (immobilization) on two occasions at the ages of 3 to 4 and 15 to 16 months. Plasma levels of the catecholamines (CA) norepinephrine (NE) and epinephrine (E) were determined before and during stress at each session. During stress, plasma NE and E levels increased markedly. At the younger age, female animals showed markedly higher CA levels than male animals. After one year, stress CA levels were higher for both sexes, but had increased markedly in male and little in female animals. A positive correlation was found between the plasma CA stress response of individual animals at both sessions; this correlation was stronger for males and NE. This indicates that "high" responders usually remain high responders, "low" responders remain low and intermediate responders intermediate. In conclusion, the plasma CA stress response increases markedly in male, but little in female rats over the period of 1 year and the relative magnitude of the individual stress response remains a characteristic of each given animal.

Age Factors

Effects of buspirone on plasma catecholamines, heart rate, and blood pressure in stressed and nonstressed rats.

The influence of buspirone upon plasma catecholamine levels, heart rate, and mean arterial blood pressure was studied in stressed and nonstressed rats. Measures were obtained directly via indwelling aortic catheters. Drug or vehicle were given acutely (10 mg/kg, IP) or twice a day for 10 days (10 mg and 20 mg/kg, SC). In nonstressed rats, a single dose of buspirone increased markedly plasma norepinephrine and epinephrine levels and decreased significantly heart rate with no effect on blood pressure. During stress, stress-induced increases in catecholamine levels were further elevated by the drug, whereas stress-induced increases of heart rate and mean arterial blood pressure were reduced. In chronically-pretreated rats, the effects of buspirone were similar to those observed after an acute injection. These effects of buspirone on plasma catecholamines are very different from those seen with other anxiolytics, whereas effects on heart rate and blood pressure are more similar.

Animals

Effect of ethanol and stress on plasma catecholamines and their relation to changes in emotional state and performance.

The "tension reduction hypothesis" of ethanol was investigated with respect to stress- and ethanol-induced changes of plasma catecholamines and their relations to changes in emotional state and performance. Twenty-two healthy male volunteers were tested under the influence of 0.8 g/kg ethanol and compared to 22 matched controls receiving a placebo drink. Stress was induced by mental arithmetic applied prior to and 45 min after fluid consumption. Plasma epinephrine (E) and norepinephrine (NE) obtained from an indwelling cannula inserted 50 min prior to stress application were determined prior to and after each stress session. Percentage changes were compared within and between groups and correlated with respective changes of emotional states and performance in mental arithmetic. While ethanol decreased performance and stress-related emotional arousal, it did not affect stress-induced changes in plasma catecholamines. Rather, the fluid (ethanol as well as placebo) increased NE levels. Emotional tension reduction was associated with low resting or average levels of E in the placebo group but this relationship was disrupted by ethanol. High NE resting levels and drink induced increases predicted emotional tension reduction with placebo but an increase in stress induced depression with alcohol. "Biochemical tension reduction" (represented by both reduced E and NE stress response) may be predicted from generally lower levels of activation and elation by alcohol but not with the placebo condition. Although performance was positively related to low NE resting levels and stress responses, no influence of alcohol on this relationship was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Relationships of plasma catecholamines to open-field behavior after inescapable shock.

Male rats with indwelling jugular catheters were exposed to inescapable shock or no shock, and ambulation and defecation were measured 24 h later in an open field. Plasma catecholamine levels were determined from blood samples taken before and during pretreatment as well as before and after testing for aftereffects on open-field behavior. Shocked animals showed higher plasma catecholamine levels during the shock session and lower locomotor activity in the open field. Open-field activity was negatively correlated in shocked animals with both plasma catecholamines before and during shock and also with plasma epinephrine before open-field testing. Defecation was only positively correlated with plasma norepinephrine before open-field testing. Thus, the reduced open-field activity after inescapable shock may indicate heightened fear or anxiety which may also be present when shocked animals are tested for their performance in more complex tasks.

Animals

MAO inhibition and the effects of centrally administered LSD, serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats.

Pretreatment with the MAO-inhibitors iproniazid, clorgyline, or deprenyl abolishes the effects of LSD on the conditioned avoidance response (CAR) in rats. The effects of serotonin (5-HT) and 5-methoxytryptamine (5-MT) are greatly potentiated by these substances. Brain levels of LSD are not affected by MAO inhibition whereas levels of 5-HT and 5-MT are significantly elevated. It is postulated that the decreased behavioral response to LSD is the result of 'MAO inhibitor-induced' changes whereas the increased response of 5-HT and 5-MT results from increased brain levels of these compounds.

5-Methoxytryptamine

Decreased platelet monoamine oxidase activity in chronic schizophrenia, shown with novel substrates.

Platelet monoamine oxidase (MAO) was kinetically evaluated in chronic schizophrenics and matched controls, using substrates of major physiologic importance and substrates of particular interest in the study of schizophrenia, such as serotonin (5-ht), N,N-dimethyltryptamine (DMT), 5-methoxytryptamine (5-MT), and dopamine (DA). Substrates were measured at six concentrations; values for maximal velocity (Vmax) and Michaelis constant (Km) were obtained by using Lineweaver-Burk plots. The Vmax was decreased for all substrates in chronic schizophrenia and the Km was decreased for DA, 5-HT, and DMT, but remained unchanged for 5-MT. The value of Km/Vmax was similar for schizophrencis and normal persons when DA, 5-HT, and DMT were used as substrates, which may indicate that "uncompetitive" inhibition is responsible for the observed decrease in activity among chronic schizophrenics. The finding of a decreased Vmax but unchanged Km with 5-MT would be consistent with noncompetitive inhibition.

5-Methoxytryptamine