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Effects of carbamate, BPMC, on the central cholinergic functions and behavior of mice
Abstract:
O-sec-butylphenyl methylcarbamate (BPMC), an anticholinesterase carbamate, was injected once (100 mg/kg, s.c.) or repeatedly (50 mg/kg/day for 10 days) into mice. Animals were examined for their behavior and for parameters of cholinergic activity in the forebrain. Mice that received only a single injection exhibited reduced ambulation, hypothermia, and impairment of rotarod performance for up to 3 hr after a single injection. BPMC increased levels of acetylcholine (ACh) in the forebrain for up to 6 hr, and decreased acetylcholinesterase (AChE) activity for up to 24 hr. Both high-affinity choline uptake (HACU) and binding of [3H]quinuclidinyl benzilate (QNB) were reduced 20 min after a single injection without any effect on choline acetyltransferase (ChAT) activity. In behavioral tests conducted 10 min prior to the daily injections, rotarod performance and ambulation were slightly impaired for a few days before and after cessation of injection. Repeated treatment decreased HACU and binding of [3H]QNB for 24 hr after the final injection without any changes in levels of ACh content, AChE activity and ChAT activity. BPMC may reversibly impair cholinergic functions through effects not only on AChE activity but also on HACU and binding of [3H]QNB.