Interactions of Subsymptomatic Doses of Sarin with Pyridostigmine - Neurochemical, Behavioral, and Physiological Effects

摘要

This report describes the effects of treatment of male Sprague- Dawley rats with low levels of the cholinesterase (ChE) inhibitors Sarin (0.5 LD50 s.c. 3 times weekly) and pyridostigmine bromide (PB, 80 mg/L in drinking water) alone or in combination for 3 weeks as compared with untreated controls. The work during this reporting period included analysis of locomotor activity (LA) and autonomic control of heart rate (HR), as well as the metabolism of acetylcholine (ACh) and choline (Ch), at 2, 4 and 16 weeks after exposure to the ChE inhibitors. HR, derived from electrocardiogram, and LA were studied by radiotelemetry of animals in their home cages 24 hrs a day, during one week. ChE inhibitors decreased HR and enhanced HR variability 2 weeks post-treatment, but the effects did not persist until later times. No treatment-related changes in LA were found. The expected regional variations in ACh, ACh turnover, and D4Ch, similar to the distribution of other cholinergic markers, or related to characteristics of the blood-brain barrier were found, but ACh and Ch contents were altered only at two weeks post-treatment. No treatment-related effects were detected in ACh turnover. In conclusion, changes in the variables under study were mainly observed 2 weeks after treatment but failed to persist until later intervals. Thus, these experiments do not support the hypothesis that exposure to low levels of cholinesterase inhibitors could induce persistent or delayed effects in control of heart rate and locomotion or cholinergic metabolism.