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

Abstract

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.

The Toxicity Profile of a Single Dose of Paroxetine: An Alternative Approach to Acute Toxicity Testing in the Rat

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