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J.Health Sci., 45(4), 191-202, 1999
Effects of a Central Anticholinesterase, Methanesulfonyl Fluoride on The Cerebral Cholinergic System and Behavior in Mice : Comparison with an Organophosphate DDVP
Haruo Kobayashi,*,a Takuma Nakano,a Donald E. Moss,b and Tadahiko Suzukia
aPharmacology, Departments of Veterinary Medicine, Faculty of Agriculture, Iwate University, Ueda, Morioka 020-8550, Japan and bPsychobiochemistry, Department of Psychology, University of Texas at El Paso, Texas 79968, U.S.A.
Mice were injected with an anticholinesterase, methanesulfonyl fluoride (MSF, 1.5 mg/kg) or O,O-dimethyl O-(2,2-dichlorovinyl) phosphate (DDVP, 10 mg/kg) singly or repeatedly and examined for synaptic activities on the cerebral cholinergic system and behavior. MSF inhibited the activity of cerebral acetylcholinesterase (AChE) more slowly but more irreversibly than DDVP. Although a single injection of DDVP increased the concentrations of total, extraterminal, intraterminal and cytoplasmic acetylcholine (ACh) remarkably shortly after injection, MSF was still as effective at 24 h as 3 h after administration in increasing the concentrations of fractional ACh.
Repeated injection of MSF for 3 d showed a significant reduction in the activity of AChE one day after cessation with a slight recovery 5 d later. Repeated administration of DDVP for 10 days showed a less significant reduction in the activity of AChE one day after cessation with considerable recovery 14 d later.
Although a single injection of DDVP showed suppressive effects on locomotor activity, rectal temperature and rotarod performance in mice, the administration of MSF did not produce any significant effects, while DDVP suppressed locomotor activity and rectal temperature during and after the term of repeated injection. MSF showed a significant suppressive effect only at the 3rd day without causing any other changes during or after the term of repeated injection. In conclusion,
MSF causes similar, but longer lasting effects on cholinergic mechanisms than DDVP and has fewer suppressive effects on behavioral parameters than DDVP.
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