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Behavioral toxicology of acute trimethyltin exposure in the mouse
Abstract:
Adult BALB/c mice were injected IP with trimethyltin . HCl (TMT), and the effects of TMT were studied on gross behavior, lethality, spontaneous motor activity (SMA), and responding under a multiple fixed-ratio 30, fixed-interval 600 sec (mult FR30 FI600) schedule of reinforcement. Following doses of 4, 5, and 6 mg/kg, the cumulative 48-hr lethality was 10% at 4 mg/kg, IP, and 100% at 5 and 6 mg/kg, IP. No deaths were observed during the first 48 hrs following 3 mg/kg TMT. This non-lethal dose produced whole body tremors. The SMA of mice receiving 3 mg/kg was reduced to 70% during the first 24-hr period following TMT and some recovery of total activity was observed during the second 24-hr period. The reduction in SMA was accompanied by a change in the normal circadian cycle of activity. Responding under the mult FR30 FI600 schedule was severely disrupted. Three hours after TMT administration and rate of responding in both components was decreased and the decrease became progressively larger over the next 48 hrs. In addition to the rate of FI600 responding being reduced, the normal pattern of FI responding was altered with an increase in responding observed in the early portions of the FI. These results suggest that the mouse is much more sensitive to the effects of TMT than the rat and may have potential as an animal model in the study of the neurotoxicity of TMT.
Insights
Trimethyltin hydrochloride (TMT) significantly impacts mouse behavior and lethality, even at non-lethal doses. Mice exhibit tremors, reduced motor activity, and disrupted operant responding, suggesting TMT
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Trimethyltin hydrochloride (TMT) is a neurotoxicant.
- Understanding TMT's effects in animal models is crucial for assessing human health risks.
Purpose of the Study:
- To investigate the neurotoxic effects of TMT in adult BALB/c mice.
- To evaluate TMT's impact on behavior, lethality, spontaneous motor activity (SMA), and operant responding.
Main Methods:
- Mice were administered varying doses of TMT (3-6 mg/kg) intraperitoneally (IP).
- Gross behavior, lethality, SMA, and performance on a multiple fixed-ratio 30, fixed-interval 600 sec (mult FR30 FI600) schedule were assessed.
- Behavioral changes and circadian activity patterns were monitored over 48 hours.
Main Results:
- Lethality ranged from 10% at 4 mg/kg to 100% at 5-6 mg/kg TMT.
- A non-lethal dose (3 mg/kg) induced tremors and reduced SMA by 70% in the first 24 hours.
- TMT disrupted operant responding, decreasing response rates and altering patterns in both FR and FI components.
Conclusions:
- Mice are highly sensitive to TMT neurotoxicity compared to rats.
- TMT significantly impairs motor activity and cognitive functions related to operant behavior.
- Mice may serve as a valuable animal model for studying TMT-induced neurotoxicity.