Triadimefon, a triazole fungicide, induces stereotyped behavior and alters monoamine metabolism in rats

Q. David Walker, Mark H. Lewis, Kevin M. Crofton, Richard Mailman

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Triadimefon, a triazole fungicide, has been observed to increase locomotion and induce stereotyped behavior in rodents. The present experiments designed to characterize the stereotyped behavior induced by triadimefon used a computer-supported observational method, and tested the hypothesis that these observed effects involved central dopaminergic systems. Adult male and female Sprague-Dawley rats were injected with triadimefon (0, 50, 100, and 200 mg/kg) in corn oil (2 ml/kg ip) 4 hr prior to behavioral assessment. The two lowest doses of triadimefon increased the frequency of locomotion and rearing, while the highest dose induced highly stereotyped behaviors, including backward locomotion, circling, and head weaving. Immediately after behavioral testing, the rats were sacrificed, and the striata and olfactory tubercles, terminal fields of the nigrostriatal and mesolimbic dopamine systems, respectively, were removed. Steady-state concentrations of the monoamines dopamine and serotonin and their metabolites were determined by HPLC-EC. In independent experiments, the direct effects of triadimefon on dopamine (D1 and D2) receptor binding and dopamine-sensitive adenylate cyclase activity were assessed in vitro using rat striata. Dopamine concentrations were increased in olfactory tubercles, but decreased in striatum. Concentrations of 5-hydroxyindoleacetic acid (the major metabolite of serotonin) were increased only in striatum, and only in animals treated with 200 mg/kg triadimefon. In vitro, triadimefon neither competed with D1 or D2 dopaminergic radioligands nor affected dopamine-stimulated adenylate cyclase activity. Together these behavioral and biochemical data lend support to the hypothesis that triadimefon may have actions similar to those produced by indirect-acting dopamine agonists.

Original languageEnglish (US)
Pages (from-to)474-485
Number of pages12
JournalToxicology and Applied Pharmacology
Volume102
Issue number3
DOIs
StatePublished - Mar 1 1990

Fingerprint

Stereotyped Behavior
Fungicides
Triazoles
Metabolism
Rats
Dopamine
Locomotion
Metabolites
Adenylyl Cyclases
Serotonin
Dopamine D1 Receptors
Hydroxyindoleacetic Acid
Corn Oil
Dopamine D2 Receptors
triadimefon
Dopamine Agonists
Sprague Dawley Rats
Rodentia
Animals
Experiments

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Toxicology

Cite this

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abstract = "Triadimefon, a triazole fungicide, has been observed to increase locomotion and induce stereotyped behavior in rodents. The present experiments designed to characterize the stereotyped behavior induced by triadimefon used a computer-supported observational method, and tested the hypothesis that these observed effects involved central dopaminergic systems. Adult male and female Sprague-Dawley rats were injected with triadimefon (0, 50, 100, and 200 mg/kg) in corn oil (2 ml/kg ip) 4 hr prior to behavioral assessment. The two lowest doses of triadimefon increased the frequency of locomotion and rearing, while the highest dose induced highly stereotyped behaviors, including backward locomotion, circling, and head weaving. Immediately after behavioral testing, the rats were sacrificed, and the striata and olfactory tubercles, terminal fields of the nigrostriatal and mesolimbic dopamine systems, respectively, were removed. Steady-state concentrations of the monoamines dopamine and serotonin and their metabolites were determined by HPLC-EC. In independent experiments, the direct effects of triadimefon on dopamine (D1 and D2) receptor binding and dopamine-sensitive adenylate cyclase activity were assessed in vitro using rat striata. Dopamine concentrations were increased in olfactory tubercles, but decreased in striatum. Concentrations of 5-hydroxyindoleacetic acid (the major metabolite of serotonin) were increased only in striatum, and only in animals treated with 200 mg/kg triadimefon. In vitro, triadimefon neither competed with D1 or D2 dopaminergic radioligands nor affected dopamine-stimulated adenylate cyclase activity. Together these behavioral and biochemical data lend support to the hypothesis that triadimefon may have actions similar to those produced by indirect-acting dopamine agonists.",
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Triadimefon, a triazole fungicide, induces stereotyped behavior and alters monoamine metabolism in rats. / Walker, Q. David; Lewis, Mark H.; Crofton, Kevin M.; Mailman, Richard.

In: Toxicology and Applied Pharmacology, Vol. 102, No. 3, 01.03.1990, p. 474-485.

Research output: Contribution to journalArticle

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