Pre- and postweaning indices of neurotoxicity in rats: Effects of triethyltin (TET)

Abstract

Pre- and postweaning measures of learning and locomotor activity were used as indices of CNS function after early pernatal neurotoxic insult. Triethyltin (0.0, 3.0, or 6.0 mg/kg, ip) administered on Postnatal Day 5 (PND5) was used as the neurotoxicant. Learning deficits and alterations in locomotor activity were observed during both the pre- and postweaning periods. Preweaning learning ability was evaluated with an appetitive alleyway paradigm, while an automated radial-arm maze (RAM) was used to assess juvenile learning. Preweaning open-field locomotion was evaluated in the presence and absence of homecage litter while postweaning activity was measured in an automated device, the Motron, or as a component of performance in the RAM. The 6.0-mg/kg TET-exposed animals required more trials to acquire the alleyway task. RAM subjects receiving 6.0 mg/kg of TET were less accurate than those given 3.0 mg/kg or vehicle control. TET did not affect open-field activity on PND10; low levels of spontaneous locomotion occurred regardless of treatment. On PND13, there was a dose-related decrease in locomotion over home-cage litter while all groups exhibited equivalent low rates of locomotion in the absence of home-cage cues. All treatment groups were more active when tested over litter than over no litter. In contrast, on PND21 and throughout the RAM testing period, TET-exposed subjects exhibited dose-related increases in activity. TET produced treatment-related decreases in wet weight of whole brain, hippocampus, and cerebellum in both developing (PND23) and adult (PND200) animals with the hippocampus being most affected on a percentage basis. In contrast, no treatment-related body weight differences were observed at these times. The neurotoxicity of TET can be demonstrated during the preweaning period whether a commonly used endpoint in assessing CNS function (locomotor activity) is monitored or a more complex endpoint (learning) is evaluated provided (1) the method used to monitor locomotor activity incorporates both the normally low levels of preweaning locomotion and the more elevated levels induced by home-cage cues and (2) the learning paradigms utilized are appropriate for the capabilities of the animal.