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Nitrile-induced behavioral abnormalities in mice
H Tanii1, M Hayashi, K Hashimoto
1Department of Hygiene, School of Medicine, Kanazawa University, Japan.
Abstract:
A single oral dose of crotononitrile or 2-pentenenitrile induced behavioral abnormalities such as circling, hyperactivity and head twitching. Crotononitrile induced the abnormalities in both olive oil- and CCl4 pretreated mice, whereas 2-pentenenitrile induced the abnormalities only in CCl4-pretreated mice. Seven related compounds induced no behavioral abnormality. The head twitching by crotononitrile and 2-pentenenitrile was either reduced by treatment with serotonin and dopamine antagonists, or enhanced by a serotonin releaser, suggesting that both the serotonin and dopamine systems are involved in the behavioral abnormalities induced by these two nitriles.
Insights
Crotononitrile and 2-pentenenitrile cause behavioral changes in mice. These effects involve both serotonin and dopamine systems, indicating their role in nitrile-induced neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
Background:
- Nitriles are industrial chemicals with potential neurotoxic effects.
- Understanding the specific mechanisms of nitrile neurotoxicity is crucial for risk assessment.
Purpose of the Study:
- To investigate the neurobehavioral effects of crotononitrile and 2-pentenenitrile in mice.
- To explore the involvement of serotonin and dopamine pathways in these observed effects.
Main Methods:
- Administration of single oral doses of crotononitrile and 2-pentenenitrile to mice.
- Pretreatment with olive oil or carbon tetrachloride (CCl4).
- Assessment of behavioral abnormalities and manipulation of neurotransmitter systems using antagonists and releasers.
Main Results:
- Crotononitrile induced behavioral abnormalities (circling, hyperactivity, head twitching) in both olive oil- and CCl4-pretreated mice.
- 2-pentenenitrile induced abnormalities only in CCl4-pretreated mice.
- Head twitching was modulated by serotonin and dopamine antagonists and a serotonin releaser, implicating these neurotransmitter systems.
Conclusions:
- Crotononitrile and 2-pentenenitrile exhibit distinct neurobehavioral toxicity profiles in mice.
- Serotonin and dopamine systems play a significant role in the head-twitching behavior induced by these nitriles.