Effects of Amitraz on Motor Function *

Abstract

The effects of amitraz, a formamidine derivative, on motor function were studied in rats. Behavioural and neurochemical studies were performed. Results show that amitraz was able: 1) to decrease locomotion and rearing frequencies of rats and to increase their immobility time in an open-field; 2) to displace to the left the control dose-response curve constructed to apomorphine-induced stereotyped behavior; 3) to potentiate both pentobarbital sleeping time and amphetamine effects on open-field behaviour of rats and 4) to increase not only the whole brain levels of noradrenaline but also the striatal levels of dopamine. In relation to control animals, the pesticide also induced 5) a decrease in the striatal levels of homovanillic acid, 6) pesticide effects on open-field behaviour of rats were not antagonized by yohimbine administration, and 7) metoclopramide administration on amitraz pretreated rats antagonized not only amphetamine effects on open-field behaviour, but also apomorphine-induced stereotypy. These results are discussed in the light of the actions of amitraz on biogenic amines. It is suggested that the pesticide effects on motor function are consequences of the inhibitory effects on MAO activity, most probably through the increases produced on catecholamine levels within the central nervous system.

Amitraz changes NE, DA and 5-HT biosynthesis and metabolism mediated by alterations in estradiol content in CNS of male rats

“…Moreover, in addition to its well-documented role in the neural control of reproduction, E2 modulates such neural functions such as affect, anxiety, mood, fear and cognitive function, as well as learning and memory (Jacome et al, 2010). Therefore, the behavioral effects of amitraz including hyperreactivity to external stimuli, aggressiveness, and motor incoordination (Florio et al, 1993) could be mediated by the alterations observed in the enzymes regulating catecholamines and indoleamines synthesis and metabolism. Otherwise, low levels of MAO expression in the brain result in a , prefrontal cortex (FC) and striatum (ST) from adult male rats.…”

“…Moser and MacPhail (1989) reported that amitraz inhibits MAO only at doses of 100 mg/kg bw, so this mechanism could not explain the effect seen at lower doses. However, motor incoordination appears from doses lower than 100 mg/kg bw (from 6.25 to 25 mg/kg bw/day) in rats (Moser et al, 1987), and it has been reported that MAO inhibition mediates motor incoordination (Florio et al, 1993), suggesting this enzyme could mediate the monoamine neurotransmitters alteration observed at doses lower than 100 mg/kg bw.…”

“…Food from treated group was removed 6 h before treatment, but animals were allowed water ad libitum. The doses of 20, 50 and 80 mg/kg bw [equivalent to 1/30, 1/12 and 1/7.5 of the LD 50 (mean LD 50 was previously calculated, data not shown)] were chosen because they were previously described to produce a dose-dependent alteration of monoamine neurotransmitters 5-HT, NE, DA and their metabolites after 5 consecutive days of treatment (Del Pino et al, 2013) and because they are under the doses that have been reported to inhibit MAO (Moser and MacPhail, 1989), which was the mechanism suggested to produce this alteration (Florio et al, 1993). Thus, the selected doses are relevant to study the mechanisms of alteration of these monoaminergic neurotransmitters.…”

“…Therefore, amitraz could mediate the effects observed on monoaminergic neurotransmitters by blocking MAO. In this regard, Florio et al (1993), showed that amitraz at dose of 100 mg/kg bw increased NE and DA levels in hypothalamus and striatum, respectively, and decreased the homovanillic acid (HVA) levels in striatum and attributed these effects to MAO inhibition. Moser and MacPhail (1989) reported that amitraz inhibits MAO only at doses of 100 mg/kg bw, so this mechanism could not explain the effect seen at lower doses.…”

Intoxicações natural e experimental por amitraz em eqüídeos: aspectos clínicos

“…A inibição da enzima monoaminoxidase (MAO, tipos A e B), que provocaria uma diminuição na metabolização da noradrenalina, também tem sido defendida como causa principal dessa intoxicação (Aziz & Knowles 1973, 1992, Florio et al 1993, Benezet & Knowles 1976. A metabolização das catecolaminas e indolaminas necessita de uma desaminação oxidativa, processo enzimático realizado pelas monoaminoxidases .…”