Accession Number:

ADA503042

Title:

Cerebral Acetylcholine and Choline Contents and Turnover Following Low-Dose Acetylcholinesterase Inhibitor Treatment in Rats

Descriptive Note:

Technical rept. Feb 2000-Feb 2004

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2006-05-01

Pagination or Media Count:

21.0

Abstract:

Rats were treated for three weeks with regular drinking water plus subcutaneous sc saline 0.5 mlkg injections three timesweek pyridostigmine bromide PB in drinking water 80 mgL plus sc saline injections three timesweek regular drinking water plus sc sarin 0.5 x LD50 injections three timesweek or PB in drinking water plus sc sarin injections three timesweek. Repeated doses of sarin, with or without PB, were devoid of acute toxicity during the three-week treatment period. Two, 4, and 16 weeks post-treatment, animals were given an intravenous pulse injection of choline labeled with 4 deuterium atoms D4Ch followed, 1 min later, by microwave fixation of the brain in vivo. Tissue levels of endogenous acetylcholine D0ACh, endogenous choline D0Ch, D4Ch, and ACh synthesized from D4Ch D4ACh were measured by GC-MS in hippocampus, infundibulum, mesencephalon, neocortex, piriform cortex, and striatum. Ch uptake from blood and ACh turnover were estimated from D4Ch and D4ACh concentrations in brain tissue, respectively. Statistically significant differences among brain regions were found for D0Ch, D4Ch, D0ACh and D4ACh at 2, 4 and 16 weeks post-treatment. Differences in these parameters between control and drug treatments were found only for D0ACh and D0Ch at 2 and 4 weeks. The results from these experiments do not support a delayed or persistent alteration in cholinergic function after exposure to low doses of PB andor sarin.

Subject Categories:

  • Biochemistry
  • Toxicology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE