Effect of chronic pyridostigmine bromide treatment on cardiovascular and behavioral parameters in mice

Abstract

Experiments were performed to determine the effect of chronic low-dose pyridostigmine bromide (PB) treatment on blood acetylcholinesterase (AChE), cardiovascular (CV) function, and behavior in C57BL/6J male mice. Chronic carotid arterial catheters were used for long-term CV measurements and for collection of blood samples. Separate groups of mice were used for behavioral open field tests. PB was administered subcutaneously using osmotic minipumps at 1 and 3 mg/kg/day for 7 days. Blood pressure and heart rate (HR) were measured continuously for 24 h before treatment and on Days 3 and 7 after minipump insertion. Blood samples were collected on the same days. Mean arterial pressure (MAP) of the control group was 108±2 and 104±2 mm Hg during the dark and light periods, respectively. HR was 510±18 and 493±19 beats/min during the dark and light periods, respectively. PB treatment had no effect on MAP or HR in either dark or light period. Basal AChE activity was 0.42±0.1 μmol/min/ml, with no changes observed with PB at 1 mg/kg/day. The higher PB dose (3 mg/kg/day) decreased blood AChE activity by 85% on Day 7. Despite the reduction in blood AChE activity, there were no alterations in open field behaviors (locomotor activity, rearing, distance traveled, rest time, number of entries, and pokes). In conclusion, chronic low-dose PB exposure decreased blood AChE activity but had no effect on CV function or behavior in mice.