Delayed behavioral and endocrine effects of sarin and stress exposure in mice.
The organophosphorus agent sarin is a potent inhibitor of acetylcholinesterase. Experiments tested the influence of exposure to low doses of sarin along with psychological stress on delayed behavioral and endocrine changes in mice. Motor activity, acoustic startle response (ASR), pre-pulse inhibition (PPI) of ASR, activity of cholinesterase in blood and catecholamine levels in adrenals were evaluated after low dose sarin exposure (3 x 0.4 LD50 subcutaneously) combined with chronic intermittent stress in C57BL/6J mice. While sarin alone produced depression of motor activity, no interaction of the stress with sarin exposure was observed. Cholinesterase activity was significantly reduced 24 h after exposure to sarin; however, the basal activity was re-established 3 weeks later. The combination of low dose sarin exposure and stress produced delayed behavioral change manifested as excessive grooming together with endocrine alterations in adrenals 7 weeks after exposure. The size of the adrenals in the combined exposure group was increased and the concentration of catecholamines was significantly decreased. In conclusion, these findings indicate that sarin in low doses is more dangerous when combined with shaker stress inducing delayed behavioral and endocrine changes.
Mach
Mojmir
M
Wright State University, Boohnshoft School of Medicine, Dayton, OH 45435, USA. mojmir.mach@savba.sk
Grubbs
Robert D
RD
Price
William A
WA
Nagaoka
Maya
M
Dubovický
Michal
M
Lucot
James B
JB
D000161:Acoustic Stimulation; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D018923:Persian Gulf Syndrome / Q000378:metabolism / Q000523:psychology; D013216:Reflex, Startle / Q000187:drug effects; D012524:Sarin / Q000633:toxicity*; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D002395:Catecholamines; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D012524:Sarin; D002802:Cholinesterases