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Biomedical subjects

S C Dilsaver

Publications and source records attributed to S C Dilsaver.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1990

Effects of bright light on responsiveness to a muscarinic agonist in rats selectively bred for endogenously increased cholinergic function.

The Flinders Sensitive Line (FSL) was derived from the Sprague-Dawley rat by selectively breeding those animals exhibiting a high level of sensitivity to an anticholinesterase. The Flinders Resistant Line (FRL) was simultaneously developed as a control line. These lines exhibit nonoverlapping distributions of their thermic responsiveness to oxotremorine. Bright light prevents the development of supersensitivity to oxotremorine occurring as a result of forced stress or treatment with a muscarinic receptor antagonist in the rat. The authors now report that treatment with bright light during the regular photoperiod (i.e., a time that does not produce a phase-shift or free-running) differentially affects the hypothermic response and activity-suppressing effect of oxotremorine in both the FSL and FRL. Both lines exhibit decreased hypothermia without reduction in motor activity in response to oxotremorine following 6 days of treatment with bright light. The magnitude of blunting of the hypothermic response was greater in the FSL than the FRL. These findings suggest that (1) studies of the effects of bright light are contingent on the end point one measures and (2) the capacity of this treatment to blunt the hypothermic response to a muscarinic agonist is greater in an animal model with endogenously hyperactive muscarinic cholinergic systems.

Animals↗
PubMed1990

From phenomenon to mechanism: an investigational strategy.

1. The author describes an investigational strategy useful in the field of psychopharmacology. 2. This strategy is based on the ability of a multi-disciplinary team first to measure significant changes in a behavioral or physiological variable in response to an experimental manipulation. 3. This initial measurement allows investigators to identify a phenomenon but not its underlying mechanism. 4. Study then proceeds to assess the anatomical substratum essential to mediating the physiologic change and receptology. 5. Finally, changes in second messenger mechanisms are determined. 6. Study of the neurobiologic effects of bright light is used as an illustration.

Animals↗
PubMed1990

Chronic treatment with ethanol produces supersensitivity to oxotremorine.

1. The effect of chronic treatment with ethanol (14% v:v in drinking water) on the physiological endpoint core temperature which is partially regulated by a muscarinic mechanism was measured in adult male rats (n = 8). 2. One and two weeks of treatment were associated with enhancement of the hypothermic response to oxotremorine, 0.25 mg/kg ip (p = 0.0005 and p = 0.0001, respectively). 3. The sample remained supersensitive to this muscarinic agonist 48 and 96 hours after the discontinuation of treatment (p = 0.0014 and p = 0.013 respectively). 4. Repeated injections of oxotremorine, 0.25 mg/kg ip, every other day for 10 days did not produce carry-over effects in a control experiment. 5. The results suggest that ethanol renders muscarinic mechanisms supersensitive during chronic treatment and that supersensitivity remains up to 96 hours following withdrawal.

Animals↗
PubMed1990

Effects of placebo (saline) injections on core temperature in the rat.

1. Core temperature was telemetrically measured in 15 rats before (i.e., at baseline) and at 10-min intervals for 120 min following the injection of normal saline (1 ml/kg ip) or "no injection." 2. The sample exhibited a mean temperature increase of 0.60 +/- 0.10 degree C (mean +/- SEM) following injection. 3. This differed significantly from the mean increase of 0.13 +/- 0.03 degree C following "no injection" (p less than 0.001). 4. The injection of saline (1 ml/kg) affected a mean rise in core temperature of 0.55 +/- 0.07 degree C (p greater than 0.000001) in 46 animals in a second experiment. 5. These data indicate that routine handling and a simple injection comprise significant and measurable stress which must be controlled in neuropharmacological studies employing a thermoregulation paradigm.

Animals↗
PubMed1990

Heterocyclic antidepressant, monoamine oxidase inhibitor and neuroleptic withdrawal phenomena.

1. The authors review the literature describing acute symptomatology produced by the gradual or abrupt withdrawal of heterocyclic antidepressants, monoamine oxidase inhibitors (MAOI) and neuroleptics. 2. Withdrawal of heterocyclic antidepressants and antipsychotic agents causes similar symptomatology. Symptoms produced by the discontinuation of these drugs include nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgias, paresthesias, anxiety, agitation, restlessness, and insomnia. 3. Psychotic relapse is often presaged by anxiety, agitation, restlessness, and insomnia. Prodromal symptoms are distinguished from the effects of neuroleptic withdrawal by a temporal relationship of the latter to reductions in the dosage or discontinuation of antipsychotic agents. 4. Withdrawal of MAOIs can result in severe anxiety, agitation, pressured speech, sleeplessness or drowsiness, hallucinations, delirium, and paranoid psychosis. 5. MAOI withdrawal phenomena resemble the symptoms produced by the discontinuation of chronically administered psychostimulants. 6. The capacity of MAOIs to exert amphetamine-like effects presynaptically and the propensity of somatic treatments for depression to subsensitize presynaptic receptors regulating the release of catecholamines provide a basis for the development of psychotic symptoms upon the withdrawal of MAOI. Evidence for this hypothesis is reviewed.

Antidepressive Agents, Tricyclic↗