Evidence for monoaminergic involvement in triadimefon-induced hyperactivity.
Triadimefon is a triazole fungicide that produces hyperactivity in both mice and rats similar to that seen following administration of compounds with catecholaminergic activity (e.g., d-amphetamine). To determine whether the triadimefon-induced hyperactivity is due to an action on CNS catecholaminergic systems, we evaluated the effects of combined treatment of triadimefon with either the tyrosine hydroxylase inhibitor d,l-alpha-methyl-p-tyrosine methyl ester HCl (alpha MPT) or the amine depletor reserpine. Adult male Long-Evans hooded rats, approximately 70 days of age were used. Dosage-effect functions were determined for alpha MPT (0-200 mg/kg IP), reserpine (0-2.5 mg/kg IP), d-amphetamine (0-3 mg/kg IP), and methylphenidate (0-40 mg/kg IP). Motor activity was measured as photocell interruptions in figure-eight mazes. The interaction between triadimefon and alpha MPT was determined with the following groups: 1) vehicle control; 2) 200 mg/kg triadimefon PO; 3) 100 mg/kg alpha MPT; and 4) both alpha MPT and triadimefon. A similar design was used to determine the interaction between triadimefon and reserpine (0.62 mg/kg), alpha MPT and d-amphetamine (1.5 mg/kg), and reserpine and methylphenidate (5.0 mg/kg). In the first experiment alpha MPT did not block the increased motor activity produced by triadimefon (i.e., both triadimefon alone and alpha MPT in combination with triadimefon produced significant increases in motor activity). alpha MPT did, however, block d-amphetamine-induced hyperactivity. Since alpha MPT did not antagonize the effect of triadimefon, these data suggest that increased motor activity produced by triadimefon is not mediated through release of newly synthesized catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
Crofton
K M
KM
Neurotoxicology Division, US Environmental Protection Agency, Research Triangle Park, NC 27711.
Boncek
V M
VM
MacPhail
R C
RC
D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D003913:Dextroamphetamine / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000494:pharmacology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology*; D019805:alpha-Methyltyrosine
D015306:Biogenic Monoamines; D005659:Fungicides, Industrial; D008781:Methyltyrosines; D014230:Triazoles; C032910:triadimefon; D008774:Methylphenidate; D019805:alpha-Methyltyrosine; D012110:Reserpine; D003913:Dextroamphetamine