Interactions of Subsymptomatic Doses of Sarin with Pyridostigmine - Neurochemical Behavioral and Physiological Effects
Abstract
This report describes the effects of treatment with low levels of the cholinesterase (ChE) inhibitors Sarin (0.5 LD5O 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. At 2, 4 and 16 weeks after exposure, we studied neurochemical, behavioral and physiological parameters. The main findings have established: Neurochemical cholinergic markers (AChE, ChAT, and QNB binding) were not altered, except for a decrease in the expression of muscarinic receptors in some regions 2 weeks after treatment. Passive and conditioned avoidance responses as well as water maze tests showed no difference between treatments. Baroreceptor responses tested by pharmacological manipulation of arterial blood pressure were not affected by treatments. Exploration of an open field showed decrease in total distance walked in sarin treated animals 2 weeks after treatment that was not present with simultaneous PB and sarin administration. Enhancement of auditory startle was found with sarin 2 weeks after treatment, a phenomenon absent in the group in which PB was administered simultaneously with sarin. PB administration induced delayed bradycardia and decreased of heart rate variability, that were not explained by changes in locomotor activity or AChE inhibition at the time. Cerebral blood flow but not glucose utilization was enhanced 2 weeks after treatment with sarin+PB and 4 weeks after treatment with sarin. The expected regional variations in ACh, ACh synthesis rate, and D4Ch, similar to the distribution of other cholinergic markers, or characteristics of the blood-brain barrier reported in the literature were found, but no treatment related effects were detected in ACh synthesis rate. In conclusion, no consistent adverse effects of PB, or sarin, alone or in combination, have been detected following 2 to 16 weeks after low-dose chronic administration of these compounds.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA423970
Entities
People
- Donald J. Jenden
- Oscar U. Scremin
- Tsung-Ming Shih