You are here:
INVESTIGATIONS OF AMITRAZ NEUROTOXICITY IN RATS. III. EFFECTS ON MOTOR ACTIVITY AND INHIBITION OF MONOAMINE OXIDASE
Citation:
Moser, V. AND R. MacPhail. INVESTIGATIONS OF AMITRAZ NEUROTOXICITY IN RATS. III. EFFECTS ON MOTOR ACTIVITY AND INHIBITION OF MONOAMINE OXIDASE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/455 (NTIS PB91109470).
Description:
The formamidine pesticide amitraz (AMZ) produces many behavioral and physiological changes in rats. o explore possible neurochemical mechanisms for the behavioral effects of AMZ, we examined the dose effect and time course of AMZ on motor activity, monoamine oxidase (MAO) and acetylcholinesterase (AChE) activity. or motor activity studies, male Long-Evans hooded rats were tested in photocell activity measurement devices. MZ produced dose-related decreases in motor activity of rats allowed free access to food and rats maintained at a stable body weight though food restriction. owest effective doses of AMZ tested were 1-3 mg/kg, administered 20 min before testing. MZ appeared to be about 3 times more potent in food-restricted rats, indicating that amount of body fat may play a significant role in the pharmacokinetics of AMZ. otor activity returned to control levels over 4-5 days after dosing with 100-200 mg/kg AMZ, whereas recovery was evident the day after administration of low doses (1-30 mg/kg). nhibition of MAO was measured in whole brain of rats sacrificed at various time after dosing with AMZ. nly doses > 100 mg/kg AMZ inhibited MAO, which was measurable within 2 hr after dosing and lasted up to 7 days. MZ appeared to be more selective for type B MAO when given in vivo. owever, no selectivity was indicated by the IC50 values determined in vitro (IC50 = 31 uM and 28 uM for MAO-A and MAO-B, respectively). MZ produced only neglible inhibitin of AChE at the highest doses administered in vivo or al 10 uM in vitro. hese data indicated that while AMZ does inhibit MAO, the dose range over which it produced this section is much higher than that which suppressed motor activity. he dose-dependent time course was similar for both measures, however, with recovery from effects of low doses being relatively quick but on the order of days following high doses.