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Biomedical subjects

S C Dilsaver

Publications and source records attributed to S C Dilsaver.

At least 19 recordsLinked to original sources
PubMed1992

The Flinders Sensitive Line exhibits enhanced thermic responsiveness to nicotine relative to the Sprague-Dawley rat.

The Flinders Sensitive Line (FSL) was derived from the Sprague-Dawley rat by selectively breeding animals with heightened sensitivity to an anticholinesterase. The FSL now consistently exhibits enhanced behavioral and physiological responses to muscarinic agonists relative to its progenitor. The authors now report the FSL exhibits enhanced thermic responsiveness to nicotine relative to the Sprague-Dawley rat. The possible relevance of this finding to investigators interested in the disorders of mood is briefly discussed.

Animals↗
PubMed1992

Measurement of temperature in the rat by rectal probe and telemetry yields compatible results.

The change in body temperature of the rat is commonly measured using biotelemetry or the rectal probe. The authors report that the two methods yield qualitatively similar but quantitatively different results in two experiments. In Experiment 1, both methods detected a salicylate-affected reduction in handling-induced hyperthermia. In Experiment 2, both methods were useful in detecting the hypothermia induced by the muscarinic agonist oxotremorine. In both Experiments 1 and 2, measurements of baseline temperature were higher when measured with the rectal probe. Baseline temperature is measured with biotelemetry prior to handling animals, whereas the act of measuring baseline temperature with the rectal probe necessitates handling. The investigators hypothesized that a rise in baseline temperature produced by handling at least partially accounts for the greater hypothermic response obtained in Experiment 2 using measurements obtained with the rectal probe. In Experiment 3, baseline temperature was measured with biotelemetry after animals were handled. Handling produced an increase in baseline temperature. The hypothermic response to oxotremorine was increased when the higher posthandling baseline temperature was used to calculate the hypothermic response of animals. The authors conclude that differences in baseline temperature and hypothermic response obtained with the two methods are related to an effect of handling.

Animals↗
PubMed1992

Secondary social phobia in patients with major depression.

Nineteen of 42 (45.2%) patients were socially phobic when and only when depressed. Each of these patients met diagnostic criteria for primary depression (Research Diagnostic Criteria) and major depression (DSM-III-R). Every subject had three or more distinct episodes of depression. Eight of the 9 men (88.9%) and 11 of the 33 women (33.3%) were socially phobic when depressed (p = 0.004). Patients with recurrent wintertime episodes of major depression (p = 0.036) and a past history of alcohol or drug abuse were more likely to be socially phobic (p = 0.0001). The authors suggest the 19 socially phobic patients with primary depression should be regarded as having secondary social phobia. Secondary social phobia may be an important source of comorbidity in patients with primary depression.

Adult↗
PubMed1992

Chronic treatment with ethanol alters the physiological action of nicotine.

1. Ethanol decreases the release of acetylcholine through effects on presynaptic neurons at both muscarinic and nicotinic junctions. 2. Blockade of the release of acetylcholine should produce denervation supersensitivity at both muscarinic and nicotinic cholinergic junctions. 3. Chronic but not acute treatment with ethanol produces supersensitivity to the hypothermic effects of a muscarinic agonist in the rat. 4. The authors now report that chronic treatment with orally administered ethanol blunts (rather than enhances) the hypothermic response to nicotine in the rat. 5. This could have major public health implications. 6. Smoking and the use of ethanol containing beverages positively covary. 7. Ethanol induced reduction in sensitivity to nicotine suggests that the heavy consumption of ethanol may necessitate that one drink more than otherwise in order to obtain the desired effects of nicotine.

Animals↗
PubMed1992

Bidirectional effect of beta-carboline agonists at the benzodiazepine-GABAA receptor chloride ionophore complex on GABA-stimulated 36Cl- uptake.

beta-Carboline agonists produced a left shift of the GABA concentration-chloride uptake curve or a reduction in the maximal increase in GABA-stimulated 36Cl- uptake depending on their concentration. The enhancement of the GABA effect occurs only at lower beta-carboline and GABA concentrations and is smaller for the partial agonist ZK 9126 compared to the full agonist ZK 93423. The opposite effect, inhibition of GABA-stimulated chloride conductance, is observed only at higher concentrations of beta-carboline agonists and GABA. The reduction of the GABA maximal response by the partial agonist ZK 91296 is greater than by the full agonist ZK 93423. The transformation of GABA-stimulated 36Cl- uptake data to specific chloride influx (36Cl- uptake per nM of GABA) reveals that the GABA concentration-response curve consists of three parts characterized by differences in the molar effectiveness of GABA relative to the GABA concentration. The molar effectiveness of GABA is a measure of the sensitivity of the GABAA receptor chloride ionophore complex and shows adaptive changes by this complex to increasing concentrations of GABA and/or beta-carboline. We conclude from our data that the change from GABA-sensitive to GABA-insensitive conformation of the GABAA receptor occurs with increasing concentrations of GABA and/or beta-carboline. Both conformations maintain positive heterotropic cooperativity with beta-carboline binding sites, one responsible for positive and the other responsible for negative effects of beta-carboline agonists on chloride uptake.

Animals↗
PubMed1992

Differentiating organic from functional psychosis.

Psychosis is not pathognomonic of psychiatric illness. It is simply a nonspecific cluster of signs and symptoms that may occur in a broad array of medical, neurologic and surgical disorders or as a consequence of pharmacologic treatment, substance abuse or the withdrawal of drugs and alcohol. Psychoses are classified as organic or functional mental disorders. Organic disorders with psychosis are caused by structural defects or physiologic dysfunction of the brain. The causes of functional disorders have not yet been identified. Psychoses are also categorized as effective or nonaffective in character. Affective and nonaffective psychoses may be associated with either organic or functional disorders.

Affective Disorders, Psychotic↗
PubMed1992

The efficacy of bupropion in winter depression: results of an open trial.

BACKGROUND: Seasonal affective disorder (SAD) refers to regularly recurring episodes of affective illness bearing a fixed relationship to season. Wintertime depression is its most widely recognized form. This study was undertaken to assess the efficacy of bupropion as a treatment for this disorder. METHOD: Fifteen consecutively presenting patients were treated with bupropion (200 to 400 mg/day). All met DSM-III-R criteria for major depression with a seasonal pattern. All were moderately to severely depressed. A modified version of the Hamilton Rating Scale for Depression (mHAM-D) including ratings of hypersomnia, increased appetite and carbohydrate craving, and weight gain was used to quantify the severity of illness. Up to 5 weeks of treatment was allowed before the subjects were categorized as nonresponders, partial responders, or responders. RESULTS: The mean +/- SD mHAM-D scores before and after treatment were 25.5 +/- 6.4 and 4.1 +/- 3.1, respectively. Ten (66.7%) of the subjects had a complete response to treatment (mHAM-D score less than or equal to 5). The other 5 (33.3%) had a partial response (mHAM-D score = 6-10). Five of the subjects had chronic pain and 3 had panic attacks restricted to episodes of depression. These problems resolved simultaneously with the symptoms of depression. CONCLUSION: The results of this open trial suggest that bupropion is an effective treatment for winter depression. However, controlled studies are required to confidently determine whether this is the case.

Adult↗
PubMed1991

Chronic forced swim stress produces subsensitivity to nicotine.

Twice daily injections of saline reduce the thermic response to nicotine in the rat. The authors hypothesized that this was due to the stress of twice-daily handling and injection. However, the injection of saline is not a classic stressor. The hypothesis that stress blunts thermic responsiveness to nicotine was, therefore, tested using a classic form of chronic inescapable stress. Rats (n = 12) were subjected to a 14-day, twice daily course of inescapable cold water swim stress using a repeated measures design. Thermic responsiveness of nicotine was measured at baseline and every 7 days thereafter for 49 days. The mean response to nicotine (1.0 mg/kg IP) differed significantly across time, F(7,88) = 10.6, p less than 0.0001. Mean thermic responsiveness (+/- SEM) decreased from -0.75 +/- 0.09 at baseline to -0.41 +/- 0.18 degrees C (54.7% of baseline) following 14 days of forced swim stress. This change was not significant. However, the thermic response to nicotine was -0.14 +/- 0.13 degrees C (p less than 0.05), +0.55 +/- 0.12 degrees C (p less than 0.05), and +0.04 +/- 0.11 degrees C (p less than 0.05) 7, 14, and 21 days following the discontinuation of forced swim stress. The mean response did not differ from baseline 28 days following the last session of forced swim stress. The data suggest that in the recovery phase the animals ceased to be sensitive to nicotine. These findings support the hypothesis that a chronic stressor can produce subsensitivity to nicotine.

Animals↗
PubMed1991

Bright light does not alter muscarinic receptor binding parameters.

Seasonal Affective Disorders (SADs) are disorders of mood characterized by recurrent episodes of illness with a fixed relationship to season. Winter depression is characterized by recurrent onset of depression in the fall or winter followed by spontaneous recovery in the spring. This syndrome is responsive to treatment with bright light. The pathophysiology of depressive disorders may involve central muscarinic mechanisms. This possibility led to a series of physiological studies. The authors now report that contrary to expectation, treatment with bright light did not decrease the density of muscarinic receptors in either the hypothalamus or striatum.

Animals↗
PubMed1991

Arecoline-associated changes in open-field behavior following swim stress in the rat. A possible relationship to water temperature.

The rat exhibits a reduction in movement in an open field following a 14-day course of forced swim stress at 12 degrees C. The decrease in movement is greater in rats receiving arecoline relative to those receiving saline prior to placement in the open field. The authors report that when water temperature is increased to 20 degrees, there is a categorical difference in the results. The saline control group exhibits a rise and the arecoline group no change in crossings.

Animals↗
PubMed1991

Chronic treatment with amitriptyline alters the GABA-mediated uptake of 36Cl- in the rat brain.

Amitriptyline inhibits the GABA-mediated uptake of 36Cl- in membrane vesicles prepared from the cerebral cortices of drug-naive and saline-treated rats. In contrast, chronic in vivo treatment with amitriptyline affects an increase in the GABA-stimulated uptake of chloride ions in its presence. The benzodiazepine receptor antagonist ZK 93426 blocks the capacity of amitriptyline to augment the uptake of 36Cl- by 30 microM GABA. There is a possibility that there are two distinct effects of amitriptyline's action in the rat forebrain. The first is evident in vesicles from drug-naive animals and the second only after chronic treatment with this antidepressant. The authors discuss the pertinence of this finding to the mechanism of action of amitriptyline.

Amitriptyline↗
PubMed1991

Exposure to constant darkness enhances the thermic response of the rat to a muscarinic agonist.

Bright artificial light is used to treat patients with major depression with a seasonal component ("Winter Depression"). Hyperactivity of muscarinic cholinergic systems is implicated in the pathophysiology of depression. Continual exposure to bright light for 7 days or during discrete portions of the photoperiod blunts the thermic response to a muscarinic agonist (oxotremorine) in the rat. Exposure to either 24 hours per day of bright light (in contrast to periods of circumscribed exposure) or darkness would tend to produce free-running. Observers have suggested that the reduced responsiveness to oxotremorine may result from the induction of free-running (the "free-running hypothesis"). The "free-running hypothesis" leads to the prediction that rats exposed to constant darkness will exhibit a reduction in thermic responsiveness to oxotremorine. The authors hypothesized that constant exposure to darkness would, contrary to the "free-running hypothesis," enhance the thermic response to oxotremorine. Rats (n = 12) exposed to constant darkness for 7 days exhibited super-sensitivity to oxotremorine 5 days after return to standard light/dark cycle in the vivarium. This argues against the hypothesis that the induction of free-running enhances sensitivity to the thermic effects of oxotremorine.

Animals↗
PubMed1991

A nicotinic receptor antagonist enhances the hypothermic response to a muscarinic agonist.

1. Chronic treatment with amitriptyline produces supersensitivity to the hypothermic effects of the muscarinic agonist oxotremorine. 2. Chronic treatment with amitriptyline also produces supersensitivity to the hypothermic effects of nicotine. 3. Oxotremorine and other naturally occurring muscarinic agonists are also nicotinic agonists. 4. Chronic treatment with amitriptyline produces time-dependent and reversible supersensitivity to the hypothermic effects of nicotine. 5. The authors assessed the possibility that the development of supersensitivity to oxotremorine following chronic treatment with amitriptyline is related to an effect of this antidepressant on a nicotinic mechanism. 6. A nicotinic receptor antagonist would blunt (though not necessarily eliminate) enhanced sensitivity to the thermic effects of oxotremorine if the nicotinic effects of the latter are significant. 7. The simultaneous administration of mecamylamine (a peripherally and centrally active nicotinic receptor antagonist) greatly augments (rather than blunts) the hypothermic response to oxotremorine. 8. The data suggest that the oxotremorine may activate a nicotinic mechanism counterbalancing its effect on a muscarinic mechanism. 9. This is consistent with previously published reports that the activation of nicotinic and muscarinic mechanisms can exert opposite effects.

Animals↗
PubMed1991

Symptoms of major depression: acute effect of withdrawing antidepressants.

The literature is devoid of reports indicating that a reduction in the dosage or discontinuation of antidepressants of any chemical class produces symptoms of major depression within 2-4 d. Four cases suggesting that a reduction in the daily dose or withdrawal of an antidepressant may produce symptoms of major depression within hours to days are presented.

Adult↗
PubMed1990

Bright light blocks the capacity of inescapable swim stress to supersensitize a central muscarinic mechanism.

Clinical and basic researchers have proposed that muscarinic cholinergic mechanisms mediate some effects of chronic stress. Chronic inescapable (forced) swim stress depletes brain biogenic amines and is used to produce learned helplessness in rats. Behavioral and biochemical characteristics of animals in the state of learned helplessness lead some investigators to believe this condition provides a useful animal model of depression. Inescapable swim stress also produces supersensitivity to the hypothermic effect of the muscarinic agonist oxotremorine in the rat. The authors previously demonstrated that bright light potently induces subsensitivity of a central muscarinic mechanism involved in the regulation of core temperature under a variety of circumstances. They now report using a repeated measures design that inescapable swim stress of five days duration produces supersensitivity to oxotremorine (increase in thermic response of 405%). This supersensitivity is reversed within five days by treatment with bright light, despite continuation of daily swim stress. Daily inescapable swim stress was continued beyond cessation of treatment with bright light. Five days later, supersensitivity to the hypothermic effect of oxotremorine was once again evident.

Animals↗
PubMed1990

Constant exposure to darkness produces supersensitivity to nicotine.

Treatment with full-spectrum bright artificial light produces subsensitivity to the hypothermic effect of nicotine in the rat. The authors hypothesized that prolonged exposure to darkness would produce the opposite effect. The thermic responsiveness of 11 rats to nicotine (base), 0.25 mg/kg IP, was telemetrically measured at baseline, after 7 days of exposure to constant darkness, and 2, 5, and 12 days after being returned to standard vivarium conditions. Exposure to constant darkness enhanced the hypothermic response to nicotine. The sample exhibited a hyperthermic response to nicotine 2 and 5 days after being returned to the standard vivarium conditions with a 12-hour-light/12-hour-dark cycle. The magnitude of the hyperthermia observed is characteristic of the response to the injection of saline. Twelve days after return to standard vivarium conditions the thermic response of the sample was at baseline.

Animals↗
PubMed1990

Chronic swim stress enhances the motoric inhibiting effects of a muscarinic agonist.

The authors previously demonstrated that chronic inescapable swim stress and footshock increase the capacity of a fixed dose of a muscarinic agonist to produce hypothermia in the rat. This project was designed to determine whether chronic inescapable swim stress in cold water would render a low dose of a muscarinic agonist, devoid of an effect on motor behavior in the naive rat (i.e., prior to subjection to the course of swim stress), an inhibitor of mobility. The study involved two groups of rats, an experimental group which received arecoline and a control group which received saline five minutes prior to being placed in an open field. Number of crossings, the dependent variable, was measured in both groups before and after a 14-day course of twice daily inescapable swim stress of 10 minutes duration at 12 degrees C. The arecoline-treated group, as hypothesized, exhibited a significantly greater reduction in number of crossings than the saline-treated groups following the course of swim stress.

Animals↗