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Biomedical subjects

R E Butcher

Publications and source records attributed to R E Butcher.

13 recordsLinked to original sources
PubMed1979

Psychotropic drugs as behavioral teratogens.

Three psychotropic drugs were administered to pregnant rats and were then evaluated for their behavioral and reproductive effects in the offspring. Control rats received either saline or vitamin A. Prochlorperazine had the most disruptive effects on reproduction and growth, but had the least effect on behavior. Propoxyphene had no apparent effects on reproduction or growth, but produced a variety of behavioral changes. Fenfluramine was intermediate in its effects on reproduction and growth and had behavioral effects that were revealed in tests of preweaning development. The data suggest that systematic tests of behavior add important information to evaluations of reproductive toxicity that cannot, at present, be obtained by other means.

Animals↗
PubMed1979

A preliminary test battery for the investigation of the behavioral teratology of selected psychotropic drugs.

Pregnant Sprague-Dawley rats received 25 mg/kg of prochlorperazine, 20 mg/kg of fenfluramine, 75 mg/kg of propoxyphene or 200 mg/kg of diazepam daily between the 7th and 20th days of gestation. Vehicle control groups and a positive control group (vitamin A 40,000 IU/kg/day) were similarly prepared. Observations of reproductive performance were made and the offspring examined in a battery of neurobehavioral tests. Fenfluramine and prochlorperazine produced abnormalities in both the reproductive measures and neurobehavioral testing. Propoxyphene produced developmental delays and other signs of "pure" behavioral teratogenesis in that these effects were not anticipated in any of the observations of reproductive performance. Diazepam appeared to have the mildest effect on all the measurements taken. The test methods used in this study appear to be a reasonable initial approach to the development of neurobehavioral screening procedures which are comprehensive, sensitive, and usable.

Animals↗
PubMed1979

Interlaboratory comparison of behavioral testing.

New requirements by several regulatory agencies for testing the psychotoxic potential of new drugs, chemicals, and environmental contaminants raise unique problems. In order to assess intra- and interlaboratory reliability of behavioral tests a model animal maze learning procedure was designed and run in 3 cooperating laboratories. Uniform procedures were written and identical mazes were constructed. Normal control animals of identical age and sex, but of different strains, were used by the participants. A positive control group of neurologically impaired rats was run by one laboratory. Significant differences in test results among the laboratories were found. Data obtained from the positive control animals (mean errors=28.3) indicated a learning impairment statistically significant compared to the negative control data (mean errors=12.7) from any of the participating laboratories. Based on the results of this study, a reasonable standard of interlaboratory reliability in behavioral testing appears an attainable goal.

Animals↗
PubMed1978

The relationship of gestational age to vitamin A induced postnatal dysfunction.

In an effort to determine the relationship between time of administration and consequent behavioral effects on progeny, a uniform subteratogenic dose of vitamin A (80,000 I.U./KG) was administered to gravid Sprague-Dawley rats during one of five periods of gestation (days 5-7, 8-10, 11-13, 14-16 and 17-19). Offspring were examined for changes in rate of weight gain, locomotor activity and maze learning ability (T-maze with return to nest as reward and multiple T water maze escape). Vitamin A 8-10 animals were hyperactive, vitamin A 11-13 animals acquired T-maze slower than controls and both vitamin A 8-10 and 11-13 acquired water maze slower than controls. Vitamin A 11-13 animals were significnatly lighter than controls and all other vitamin A groups.

Animals↗
PubMed1977

Induced PKU in rats: effects of age and melatonin treatment.

Newborn rats injected on Days 1-8 of life with L-phenylalanine (2 g/kg) and p-chlorophenylalanine (80 mg/kg) displayed biochemical symptoms analogous to human phenylketonuria (PKU) and maze learning impairments. The behavioral effects were less evident in rats treated on Days 9-16 or 7-24. None of the symptoms observed were alleviated by simultaneous administration of melatonin (10 mg/kg/day).

Aging↗
PubMed1976

Behavioral testing as a method for assessing risk.

Behavioral effects have been found to result from the prenatal administration of substances known to be teratogenic to the CNS. These effects occur at dose levels lower than those producing gross malformations and when the agent is administered at times other than that optimal for CNS relevant technique for detecting adverse consequences of prenatal exposure to drugs and chemicals. Behavioral testing, however, also appears to have attributes that dictate a thoughtful approach to its role as a method for assessing risk, and additional research is needed to obtain usable techniques. The need for such research is intensified by the present inability to identify potential behavioral teratogens by means other than laboratory investigation.

Animals↗
PubMed1975

Biochemical effects of induced phenylketonuria in rats.

Phenylketonuria (PKU) was induced in rats by the combined feeding of 3 per cent excess phenylalanine and 0.12 per cent of p-chlorophenylalanine, an inhibitor of phenylalanine and tryptophan hydroxylases. Increased concentrations of phenylalanine and increased ratio of phenylalanine to tyrosine were demonstrated in blood from pregnant rats fed the experimental PKU diet from day 10 to 20 of pregnancy, in fetal blood and amniotic fluid of fetal animals from mothers fed the PKU diet, and in blood of rats fed the PKU diet for 28-30 days beginning at 20-21 days of age. Both phenylpyruvic acid and orthohydroxyphenylacetic acid were excreted by rats fed the PKU diet, but neither were detected in urine in animals fed either excess phenylalanine or excess inhibitor alone. Reduced serotonin concentrations were found in brains of rats fed p-chlorophenylalanine, either alone or in combination with excess phenylalanine in the PKU diet. These biochemical changes in rats with induced PKU and the behavioral changes described earlier are similar to those of the human condition. The animal model should prove useful in searching for the mechanism of the disease.

Amino Acids↗
PubMedDate not supplied

A method for measuring locomotor behavior in rodents: contrast-sensitive computer-controlled video tracking activity assessment in rats.

A newer locomotor activity system for rodents is described. The system consists of a black, ventilated test chamber, internally lighted with a ceiling mounted video camera. The camera's image is transmitted to a contrast-sensitive tracker which maps the point of highest contrast and relays the digitalized coordinates to a PC. Dedicated software stores the information and simultaneously displays a map of the tracked subject. To illustrate the system's utility, results from an experiment are presented using an established behavioral teratogen, phenytoin. Pregnant Sprague-Dawley CD rats were exposed to 0 or 200 mg/kg of phenytoin by gavage on embryonic days 7-18 and the offspring tested in the videotracker activity monitoring device. Phenytoin is known to induce hyperactivity and circling behavior in the offspring. The system revealed that phenytoin-exposed offspring that exhibit neurological impairment were hyperactive compared to controls and the effect was predominantly seen in females. These animals exhibited more section transitions and more central and peripheral activity. When peripheral activity was subdivided into that occurring along corners versus sides, it was found that corner activity represented only a small component of the group differences whereas the side component represented most of the effect. Moreover, phenytoin offspring exhibiting the circling defect were found to display a qualitatively different pattern than noncirclers or controls. Videotracking represents a different approach to the analysis of locomotor activity patterns in experimental animals compared to older methods. Two advantages of this method are higher spatial resolution and not having to pre-specify data capture intervals. Other features are detailed regional movement information and qualitative mapping of ambulatory patterns.

Analysis of Variance↗