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Neonatal exposure to trimethyltin disrupts spatial delayed alternation learning in preweanling rats
M E Stanton1, K F Jensen, C V Pickens
1Neurotoxicology Division (MD-74B), United States Environmental Protection Agency, Research Triangle Park, NC 27711.
Insights
Neonatal exposure to trimethyltin (TMT) selectively impairs spatial working memory in young rats. These cognitive deficits are detectable before weaning, indicating early developmental neurotoxicity.
Area of Science:
- Neuroscience
- Developmental Toxicology
- Cognitive Science
Background:
- Trimethyltin (TMT) is a neurotoxic organotin compound affecting the central nervous system, particularly the limbic system.
- TMT exposure disrupts learning and memory, with potential impacts on cognitive development.
Purpose of the Study:
- To investigate the earliest age at which neonatal TMT exposure causes detectable spatial working memory deficits.
- To examine the impact of TMT on cognitive development during the preweanling period.
Main Methods:
- Long-Evans rat pups were exposed to TMT (6 mg/kg) or vehicle via intraperitoneal injection on Postnatal Day 10 (PND 10).
- Cognitive function was assessed using a T-maze delayed alternation learning paradigm and a simple position discrimination task on PND 18.
Main Results:
- Rats exposed to TMT neonatally were unable to learn the delayed alternation task by PND 18.
- Both TMT- and vehicle-treated groups successfully learned the simple position discrimination task, indicating selective impairment.
Conclusions:
- Neonatal TMT exposure selectively impairs spatial working memory in developing rats.
- These deficits are evident during the preweanling period, highlighting early neurodevelopmental toxicity.
Abstract:
Trimethyltin is an organotin compound that produces marked neurotoxicity in both adult and developing animals. The limbic system is a primary CNS target site for this toxicity, and a prominent behavioral effect of TMT is disruption of learning and memory. Impairment of cognitive development has also been suggested by studies showing that rats neonatally exposed to TMT cannot perform spatial working memory tasks during adulthood. However, the question of how early in ontogeny such deficits can be detected has not been addressed. The present study examined this question with a T-maze delayed alternation learning paradigm. Long-Evans rat pups, injected IP on Postnatal Day 10 (PND 10) with 6 mg/kg TMT and tested on PND 18, were unable to learn delayed alternation in the manner shown by vehicle control pups. However, TMT- and vehicle-treated groups were both able to learn a simple position discrimination. These findings indicate a selective impairment of spatial working memory by neonatal TMT exposure and show that this impairment can be demonstrated during the preweanling period in the rat.