Biomedical subjects

S B McMaster

Publications and source records attributed to S B McMaster.

7 recordsLinked to original sources

PubMed1992

Behavioral efficacy of diazepam against nerve agent exposure in rhesus monkeys.

The possibility that nerve agents will be used on the battlefield is real. The traditional therapy against nerve agent exposure consists of pyridostigmine pretreatment and atropine-pralidoxime chloride therapy administered after nerve agent exposure. This therapy regimen is extremely effective in preventing mortality in laboratory animals exposed to multilethal concentrations of nerve agent, yet these animals often display convulsions, brain damage, and behavioral incapacitation. We report here that the addition of diazepam to the traditional therapy for nerve agent (soman) exposure not only decreases the incidence of convulsions, but also attenuates the cognitive impairments of rhesus monkeys trained on a Serial Probe Recognition (SPR) task. Monkeys which received diazepam treatment required only 6 days before their performance on the SPR task returned to presoman exposure levels, compared to nondiazepam-treated monkeys which required 15 days. Moreover, only 1 out of the 5 monkeys which received diazepam treatment suffered tonic-clonic convulsions; in contrast all 5 monkeys which did not receive diazepam treatment experienced severe convulsive episodes. These results suggest that diazepam would be an excellent adjunct to traditional nerve agent therapy to facilitate behavioral recovery from nerve agent intoxication that might be encountered by US military personnel on the battlefield or accidental organophosphate poisoning encountered in industrial or agricultural accidents.

Acetylcholinesterase↗

PubMed1989

Effects of exercise on behavioral sensitivity to carbamate cholinesterase inhibitors.

The interaction between exercise and drug response has not been studied extensively. The present study examined the relationship between both acute (15 minute) and chronic (10 week) treadmill exercise and behavioral response to the carbamates physostigmine and pyridostigmine. Rats trained on an operant task under a multi-component FR30 schedule were used to evaluate the interaction between exercise and performance following drug administration. The direct effects of both 10 weeks of exercise conditioning and a moderate exercise challenge, as well as the interaction between two were assessed. Results obtained with physostigmine show that acute exercise increased behavioral sensitivity. Chronic exercise resulted in behavioral tolerance. These results are consistent with previously reported studies of centrally acting compounds. In contrast, pyridostigmine, which has little or no central activity, produced no behavioral changes. This result was constant over exercise conditions.

Animals↗

PubMed1986

Chronic exercise produces tolerance to muscarinic antagonists in rats.

Previous work has shown that exercise can modify behavioral sensitivity to antimuscarinic compounds. The present study examined the effect of 10 weeks of endurance exercise on atropine and scopolamine potency. The behaviorally disruptive effects of these compounds were evaluated in rats trained to respond under a MULT TO FR30 schedule of reinforcement for food reward. Following 10 weeks of endurance exercise, atropine and scopolamine dose response curves were significantly altered. The ED50 values were increased 10 and 40-fold, respectively. Tolerance to atropine or scopolamine has been reported previously only in response to chronic drug administration. The present data demonstrate that non-drug factors can significantly influence behavioral response to muscarinic antagonists.

Animals↗

PubMed1985

Sensitivity of inbred mice to methylxanthines is not determined by plasma xanthine concentration.

Male CBA/J and SWR/J mice were tested with doses of caffeine, theophylline and 8-p-sulfophenyltheophylline (xanthine). Caffeine produced dose-related decreases in locomotor activity and colonic temperatures in SWR/J mice. However, caffeine produced increases in locomotor activity and failed to lower the body temperature of CBA/J mice. Theophylline produced a decrease in body temperature of SWR/J mice. Comparison of brain caffeine levels demonstrated no difference in brain pharmacokinetics. The peripherally active xanthine failed to alter body temperature at the same molar dose as that of theophylline. These data clearly demonstrate that genetic differences in the effects of methylxanthine are due to inherent differences in the central nervous system sensitivity of the two strains. The data further indicate that while differences in xanthine metabolism may occur in inbred mice, these differences are not a major factor in the acute, peak plasma level, effects of xanthines.

Animals↗

PubMed1985

Exercise-induced changes in schedule controlled behavior.

This experiment was designed to measure the direct effect of acute exercise on performance of an operant task in rats. Treadmill exercise was manipulated along two dimensions: speed and duration. Separate groups of rats (n = 12) were tested under a multi-component time-out fixed-ratio (MULT TO FR) schedule following four exercise treatments. The first group of animals (Group A) ran at a constant speed for four different periods of time. A second group (Group B) ran for a constant period of time at four different treadmill speeds. For both groups, running took place just before operant test sessions. Operant responding on test days was compared with operant responding on the immediately preceding day. Both exercise duration and exercise speed had significant effects on operant performance.

Animals↗

PubMed1985

Comparative behavioral effects of CNS cholinesterase inhibitors.

Phenylmethanesulfonyl fluoride, methanesulfonyl fluoride, and physostigmine were compared on the efficacy with which each could suppress methylphenidate-induced stereotyped gnawing, an extrapyramidal motor behavior. Whereas physostigmine produced powerful suppression of the stereotypy, the sulfonyl fluorides did not produce any clear behavioral effect. Biochemical experiments conducted with the behavioral tests demonstrated that the sulfonyl fluorides produced inhibition of whole brain, caudate, cortex, cerebellum, hippocampus and brain stem cholinesterate equal to that produced by physostigmine. The reason for the marked discrepancy between the behavioral effect of physostigmine and the sulfonyl fluorides is unknown. It is, however, clear that the effect of the various drugs on extrapyramidal motor behaviors is not a simple function of the degree to which each inhibited CNS cholinesterase.

Animals↗

PubMed1985

Changes in drug sensitivity following acute and chronic exercise.

A number of factors are known to influence drug sensitivity. These include biological variables such as genetics, age, endocrine status and gender, as well as environmental variables such as operant schedules, ambient temperature and sleep deprivation. Additional factors function as either biological or environmental variables in different situations. For example, chronic drug administration can produce tolerance and cross tolerance and function as a biological variable. Acute administration of the same compound can function as an environmental variable. The present study examined exercise as both a biological and an environmental variable influencing drug sensitivity. Chronic exercise leads to relatively long term changes in physical fitness level, and functions as a biological variable. Fitness level did not influence drug sensitivity when physically conditioned animals and non-exercised control subjects were compared under rested conditions. Mild acute exercise, an environmental variable, increased sensitivity to muscarinic antagonists in the control subjects but not in the exercise trained animals. These results indicate that exercise state should be considered as an environmental variable capable of influencing drug response and that biological fitness level modifies this effect.

Animals↗