Effects of inescapable stress and treatment with pyridostigmine bromide onplasma butyrylcholinesterase and the acoustic startle response in rats

Pyridostigmine bromide (PB) is a reversible, peripherally active inhibitor of acetylcholinesterase (AChE) activity, and is recommended by the military as a pretreatment against potential nerve gas exposure. Recent evidence su ggests that exposure to inescapable stressors allows PB to cross the blood- brain barrier, and thereby affect central AChE activity in mice. Here, we e valuated the functional impact of a stress/PB treatment interaction on acou stic startle responding and plasma butyrylcholinesterase (BuChE) activity i n male Sprague-Dawley rats. To model the treatment protocol used by the mil itary, PB was delivered in the drinking water of rats for 7 consecutive day s. The morning after the start of PB treatment, and for the next 6 days, ha lf the rats were exposed to 1 h of supine restraint stress. We therefore em ployed a 2 x 2 (stress x PB treatment) between-groups design. Exposure to s upine stress alone induced a persistent decrease in plasma BuChE activity. Further decreases in BuChE activity were not observed in rats exposed to su pine restraint and PB treatment. Exposure to stress also induced an exagger ated startle response, evident on the last day of stress and 24 h after str essor cessation. Treatment with PB alone produced an exaggerated startle re sponse over the same time period, albeit to a lesser degree. Although treat ment with PB concurrent with stress did not produce further changes in eith er BuChE activity or acoustic startle responding, stress-induced alteration s in drinking behavior (and thereby the dose of PB ingested) may have affec ted these results. Persistent stress-induced reductions in BuChE activity m ay increase the risk of adverse reactions to cholinomimetics. (C) 2000 Else vier Science Inc. All rights reserved.