Induction of Acetylcholinesterase Activity and Apoptosis in Carboxylesterase and Butyrylcholinesterase Knockout Mice Treated with Cocaine

Abstract

Background: Cocaine is a commonly used illegal recreational drug and its consumption can produce various adverse health effects in animal and clinical studies. To date no information is available on whether exposed to cocaine will result in abnormally high plasma AChE activity in animals and whether it is characteristic of apoptosis. Our goals were to examine the relationship between enhanced AChE activity and cocaine-induced apoptosis and the possible underlying mechanisms. Methods: For this purpose, carboxylesterase and butyrylcholinesterase deficient ES1-/-BChE-/- mice in strain C57BL/6 were treated intraperitoneally with 25 mg/kg cocaine daily for 8 days and sacrificed on day 9. Plasma AChE activity and body temperature were measured before and after treatment. Tissue sections from brain, heart, kidney, and liver were stained for AChE activity and apoptosis. Results: Mice had a 1°C decrease in surface body temperature at 10 min after cocaine treatment and the temperature returned to base line by 30 min. Plasma AChE activity in mice increased about 1.5-fold on days 7-8 and 1.75-fold on days 9 after cocaine treatment. More apoptotic cells were observed in liver sections of treated mice compared to controls. TUNEL-positive cells in the liver also stained heavily for AChE activity. Conclusions: AChE activity and apoptosis were both induced in carboxylesterase and butyrylcholinesterase knockout mice treated with cocaine. Their relationship might provide some novel information of cocaine-associated toxicity. Abnormally high plasma AChE activity may be an effect biomarker of cocaine exposure.