Increased hippocampal excitability produced by amitraz

Abstract

The present study characterized the effect of the formamidine pesticide, amitraz, upon hippocampal function in male Long-Evans rats. Animals were chronically prepared with a stimulating electrode in the perforant path and field potentials were recorded from a bipolar electrode situated across the granule cell layer of the dentate gyrus. Input/output functions and paired pulse inhibition were monitored in unrestrained, unanesthetized animals over a number of days following acute administration of 100 mg/kg of amitraz. Input/output functions revealed a decrease in excitatory postsynaptic potential (ESP) slope and an increase in population spike height 4 and 24 hr after treatment, with return to baseline by 48 hr. Tests of inhibition using pairs of stimulus pulses delivered at intervals ranging between 20 and 100 msec revealed a decrease in inhibition following amitraz. Both of these effects could be mimicked by administration of 0.1 mg/kg of the alpha-2 agonist clonidine, supporting this mode of action of amitraz on CNS function. These results indicate that systemic amitraz treatment produced a transient enhancement of excitatory and reduction of inhibitory processes in a CNS pathway.