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Biomedical subjects

S Alder

Publications and source records attributed to S Alder.

6 recordsLinked to original sources

Interaction between ethanol and caffeine in operant behavior of rats.

The interaction between ethanol and caffeine on operant behavior was studied in 24 water-deprived male rats trained in a discrete trial spatial alternation schedule with water as reinforcer. One single drug dose-response experiment or one dose combination of ethanol and caffeine (including the associated control treatments) was run on 4 successive days in 1 week. The four treatments of 1 week were administered to each animal in a distinct order according to the 24 possible permutations. In the single drug weeks, ethanol (0.25, 0.5, 0.75 and 1.0 g/kg IP) or caffeine (5, 10, 20, and 40 mg/kg PO) were administered 15 min before the session. In four interaction experiments all combinations of two doses of ethanol (0.5 and 1.0 g/kg IP) and two doses of caffeine (25 and 50 mg/kg PO) were employed. Ethanol and caffeine alone showed both dose-dependently decreased choice accuracy and increased response latency and passiveness. In combination, caffeine normalized the ethanol-induced alterations in ITI response rate and pause length but potentiated the effects on choice accuracy, latency and number of pauses. The results are interpreted in terms of effects of these drugs on attentional and arousal processes, and the test procedure is proposed as a screening tool for the preclinical assessment of ethanol-drug interactions.

Animals

Neurobehavioral screening in rats: validation study.

The usefulness of a neurobehavioral check-list for the detection and characterization of neurotoxic effects of chemical compounds was evaluated in rats. The animals were given single doses of the test compounds, and higher or lower doses of the substances were administered in subsequent weeks, depending on the outcome of the experiments. The testing procedure proved to be useful for detecting the neurobehavioral hazards of psychotherapeutics and other drugs with known neurobehavioral side-effects. However, the investigational technique was less satisfactory for evaluating alcohols and various neurotoxic agents. With these compounds, even repeated dosing did not improve the predictability of the testing scheme. Swimming performance was also investigated and was found to be impaired only in rats treated with neuroleptic drugs. Based on this validation study, the advantages and pitfalls of the neurobehavioral check-list approach are discussed.

Alcohols

Neurobehavioral tests in single- and repeated-dose toxicity studies in small rodents.

The discovery of neurobehavioral hazards is an important goal of the majority of the toxicological studies. Quite often it is possible to detect signs of neurobehavioral toxicity through non-instrumental observations and from the response of the animals to simple manipulations. Psychopharmacologists have long used these techniques to identify new drugs with potential usefulness as psychotropic agents. Their approach may also be applicable for the detection of neurotoxic chemicals. Based on a review of the literature and personal experience a neurobehavioral check-list is proposed which can easily be incorporated into the animal care and treatment routine used in single- and repeated-dose toxicity studies with small rodents. The instrumental tests which measure motor activity, neuromuscular functions, muscle strength, emotionality and social behavior are also discussed. The usefulness of these procedures in toxicology is not yet established. Their introduction into the testing routine creates considerable logistic difficulties and might not be compatible with good laboratory practices. Therefore, it is suggested to explore the procedures developed by psychopharmalogists and behavioral scientists and to validate them with a variety of neurobehavioral toxins. Tests which produce relevant and reproducible data may then be added to the toxicological protocols, preferably within the framework of safety pharmacology.

Animals

Microanalysis of ultrasound vocalizations of young rats: assessment of the behavioral teratogenicity of methylmercury.

An on-line real-time computer system for the analysis of ultrasound vocalizations of rats is presented. The calls of young rats are recorded by an ultrasound microphone, transformed by an amplitude envelope and a frequency to voltage converter, digitized and stored by a microcomputer. The data management and analysis of the recorded vocalizations are entirely automated, allowing a high throughput of experiments in a routine laboratory. The frequency values are analyzed with respect to number, duration, base-interval, and mean frequency of the calls. Also, the frequency distributions of the call to call intervals, the call durations and the ultrasound frequencies, as well as the power spectra of the frequency modulations, are calculated. This system was used for the assessment of the behavioral teratogenicity of methylmercury chloride. Wistar rat dams were treated with 0, 1.5 or 5 mg/l in their drinking water from two weeks prior to pairing until the end of the experiment. The ultrasound vocalizations of two female and two male offspring per litter were recorded on days 5, 7, 9, 11, 13, and 15 for one minute in a clean glass beaker cooled to 20 degrees C. Methylmercury treatment resulted in a developmental delay and an overall reduction in the number of calls, a shortening of the base-interval and the call durations, a flattening and shift of the frequency distributions, and an alteration in the development with age of the frequency distributions. The frequency modulations of the calls also differed, their power being lower (smaller frequency variation) on several occasions.

Animals