PMID- 16628397
OWN - NLM
STAT- MEDLINE
DCOM- 20070830
LR  - 20131121
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 80
IP  - 11
DP  - 2006 Nov
TI  - Cerebral acetylcholine and choline contents and turnover following low-dose 
      acetylcholinesterase inhibitors treatment in rats.
PG  - 761-7
AB  - Male Sprague-Dawley rats were treated for 3 weeks with (1) regular tap drinking 
      water plus subcutaneous (s.c.) saline (0.5 ml/kg) injections three times/week, 
      (2) pyridostigmine bromide (PB) in drinking water (80 mg/L) plus s.c. saline 
      injections three times/week, (3) regular tap drinking water plus s.c. sarin (0.5 
      x LD(50)) injections three times/week, or (4) PB in drinking water plus s.c. 
      sarin injections three times/week. Repeated doses of sarin, in the presence or 
      absence of 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, after 
      1 min, 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 gas-chromatography mass-spectrometry 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. However, differences in the values of these 
      parameters between control and drug treatments were found only for D0ACh and D0Ch 
      at 2 and 4 weeks, but not at 16 weeks post-treatment. In conclusion, the results 
      from these experiments do not support a delayed or persistent alteration in 
      cholinergic function after exposure to low doses of PB and/or sarin.
FAU - Shih, Tsung-Ming
AU  - Shih TM
AD  - Research Division, US Army Medical Research Institute of Chemical Defense, 
      Aberdeen Proving Ground, MD 21010-5400, USA. tsungming.a.shih@us.army.mil
FAU - Scremin, Oscar U
AU  - Scremin OU
FAU - Roch, Margareth
AU  - Roch M
FAU - Huynh, Ly
AU  - Huynh L
FAU - Sun, Wei
AU  - Sun W
FAU - Jenden, Donald J
AU  - Jenden DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060421
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Cholinesterase Inhibitors)
RN  - B4XG72QGFM (Sarin)
RN  - KVI301NA53 (Pyridostigmine Bromide)
RN  - N91BDP6H0X (Choline)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Choline/metabolism
MH  - Cholinesterase Inhibitors/*toxicity
MH  - Male
MH  - Pyridostigmine Bromide/toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sarin/*toxicity
EDAT- 2006/04/22 09:00
MHDA- 2007/08/31 09:00
CRDT- 2006/04/22 09:00
PHST- 2006/02/03 00:00 [received]
PHST- 2006/03/28 00:00 [accepted]
PHST- 2006/04/22 09:00 [pubmed]
PHST- 2007/08/31 09:00 [medline]
PHST- 2006/04/22 09:00 [entrez]
AID - 10.1007/s00204-006-0101-5 [doi]
PST - ppublish
SO  - Arch Toxicol. 2006 Nov;80(11):761-7. doi: 10.1007/s00204-006-0101-5. Epub 2006 
      Apr 21.