Behavioral changes in the rat after low doses of cholinesterase inhibitors.

In rats the acute effects of low doses of five cholinesterase (ChE) inhibitors were investigated in six behavioral tests. Considerable differences were found between the inhibitors studied. TEPP and sarin at doses up to 30% LD50 were without effects. In contrast, soman, physostigmine, and pyridostigmine caused effects at dose levels which did not produce overt symptoms and did not affect running speed and simple coordinated locomotion. Soman (less than or equal to 3% LD50), physostigmine (less than or equal to 4.5% LD50), and pyridostigmine (less than or equal to 10% LD50) interfered with two-way shuttlebox avoidance learning, open field behavior, and complex coordinated movements ( hurdle -stepping task). Tests of retention in a passive avoidance learning test appeared less sensitive. It is concluded that paradigms that involve higher CNS structures and require motor activity are sensitive to some ChE inhibitors at doses far below those that cause overt symptoms. The individual characteristics of ChE inhibitors play an important role. In contrast to TEPP and sarin, soman has a predominantly central effect. Further, the finding that pyridostigmine was also effective at unexpectedly low dose levels suggests that this compound may have more central actions than hitherto accepted.