Drinking behavior and the development of hypothalamic lesions from aspartame ingestion in water-restricted weanling mice.

Wealing mice that had been deprived overnight of water, or of water and diet, were offered a solution containing L-aspartyl-L-phenylalanine-methylester (APM) or monosodium L-aspartate monohydrate (MSA) as the sole source of drinking water, and/or a diet containing large amounts of APM and/or MSA for 30 min, and were killed subsequently. Only those animals exposed to concentrated (6.64% W/V) MSA solutions developed neuronal lesions in the hypothalamic arcuate nuclei. Those offered MSA in the diet only, or APM either in the diet and/or in solution, failed to develop such lesions. Apparently water-restricted weanling mice lose their ability to regulate subsequent drinking behavior, and consume hyperosmolar MSA or APM solutions whose osmolarity or sweetness would be aversive to humans. Such animals are unsuitable for the safety evaluation of APM.