Abstract |
The formamidine pesticides amitraz and chlordimeform have recently been shown to be potent proconvulsants. Two main neuroactive prosperities have been identified as mediators of formamidine neurotoxicity, alpha-2 adrenergic agonism and local anesthetic actions. These two proposed mechanisms of formamidine action were contrasted using electrical kindling of the amygdala. Male rats were administered 0.10 and 40 mg/kg of the local anesthetic lidocaine, 0, 0.01 and 0.10 mg/kg of the alpha-2 adrenergic agonist clonidine or 0.10 and 30 mg/kg chlordimeform IP, once per day. After each injection, kindling stimulation was delivered through chronically-implanted electrodes. The high dosage of chlordimeform and both dosages of lidocaine enhanced the rate of kindling development relative to controls. Afterdischarge (AD) durations were increased over the first sessions by both treatments, but the total cumulative AD did not differ from controls. Clonidine by contrast, delayed kindling development and shortened the mean AD duration over the first seven sessions. These data provide support for a local anesthetic action of chlordimeform and stand in contrast to several recent demonstrations of alpha-2 activity of formamidines as primary contributors to formamidine toxicity. (Copyright (c) Springer-Verlag 1989.) |