STUDIES ON THE MECHANISM OF AMPHETAMINE TOXICITY IN AGGREGATED MICE

¹ Departments of Pharmacology and Psychiatry, University of Utah College of Pharmacy and College of Medicine, Salt Lake City, Utah

To explore how aggregation increases amphetamine toxicity in mice, the dose of amphetamine fatal to 50% of animals (LD50) and the pentylenetetrazol seizure threshold were determined in isolated and aggregated mice. The LD50 for amphetamine in isolated mice was approximately 125 mg/kg and, except for an occasional animal, all deaths occurred within 2 hours of amphetamine administration. Aggregation increased the toxicity of amphetamine 2 to 5 times over that of the drug in isolated mice. Amphetamine was found to lower the pentylenetetrazol seizure threshold in proportion to the dose employed in both isolated and aggregated animals, but the threshold was significantly lower in aggregated than in isolated mice. Prior aggregation for periods longer than 2 hours resulted in some type of adaptation to the social situation which abolished the difference in response of isolated and aggregated mice to pentylenetetrazol.

It is concluded that aggregation in itself significantly lowers pentylenetetrazol seizure threshold. This sums with the threshold-lowering effects of amphetamine to increase markedly the toxicity of amphetamine. It is suggested that the reduction in pentylenetetrazol threshold is related to anxiety or fear induced by the sudden change in the environment of the animal. The significance of this interpretation is discussed.

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