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Abnormal behavioral effects elicited by a neurotropic mycotoxin, fumitremorgin A in mice
Abstract:
Fumitremorgin A (FTA), a neurotropic mycotoxin induced dose-dependent abnormal behaviors, including tremor, clonic convulsion, kangaroo posture and tonic extensor convulsion in the mouse. FTA-induced tonic extensor convulsion was markedly suppressed by anticonvulsant, e.g. phenobarbital, phenytoin. Phenobarbital, trimethadione, valproic acid and mephenesin decreased the occurrence of abnormal behaviors induced by FTA. Although pentylenetetrazol-induced tonic extensor convulsion was not affected by antipsychotic drugs (dopaminergic drugs) except chlorpromazine, FTA-induced abnormal behaviors were inhibited by antipsychotic drugs, e.g. chlorpromazine, haloperidol. Chlordiazepoxide, diazepam and muscimol inhibited FTA-induced abnormal behaviors. These findings suggest that both dopaminergic and gamma-aminobutyric acid (GABA)-ergic systems are involved in FTA-induced abnormal behaviors. FTA-induced abnormal behaviors may be useful as a common experimental model for the primary evaluation of anticonvulsants, antipsychotic drugs and anxiolytic drugs.
Insights
Fumitremorgin A (FTA) causes abnormal behaviors in mice, which are reduced by anticonvulsant, antipsychotic, and anxiolytic drugs. This suggests FTA-induced behaviors can model drug evaluation.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Fumitremorgin A (FTA) is a neurotropic mycotoxin.
- FTA induces dose-dependent abnormal behaviors in mice, including tremors and convulsions.
Purpose of the Study:
- To investigate the neurochemical systems involved in FTA-induced abnormal behaviors.
- To evaluate the potential of FTA-induced behaviors as a model for drug screening.
Main Methods:
- Administration of FTA to mice to induce abnormal behaviors.
- Testing the effects of various drugs, including anticonvulsants, antipsychotics, and anxiolytics, on FTA-induced behaviors.
- Assessing the involvement of dopaminergic and GABA-ergic systems.
Main Results:
- Anticonvulsants (phenobarbital, phenytoin) significantly suppressed FTA-induced tonic extensor convulsions.
- Antipsychotic drugs (chlorpromazine, haloperidol) and anxiolytics (chlordiazepoxide, diazepam, muscimol) inhibited FTA-induced abnormal behaviors.
- The results indicate involvement of both dopaminergic and GABA-ergic systems.
Conclusions:
- Dopaminergic and GABA-ergic systems play a role in FTA-induced abnormal behaviors.
- FTA-induced abnormal behaviors represent a potential experimental model for evaluating anticonvulsant, antipsychotic, and anxiolytic drugs.