Selective Inhibition of Acetylcholinesterase in the Cerebellum and Hippocampus of Mice Following an Acute Treatment with Malathion

Adult male ICR mice were treated by intraperitoneal injection with 250?mg/kg of bodyweight of commercial malathion (a dose corresponding to 1/12 the LD50). After 6?h, acetylcholinesterase (AChE) activity in blood, liver, and six brain regions was determined. A statistically significant inhibition was observed in whole blood (23%), liver (21%), and, in particular, the central nervous system; the greatest degree of AChE inhibition was observed in the cerebellum (45%), followed by the hippocampus (29%). There was no significant change in AChE activity in the caudate putamen, frontal cortex, midbrain, or pons medulla. These results demonstrate that the magnitude of AChE inhibition in peripheral tissues does not accurately reflect the central-inhibitory effects of malathion on AChE activity in specific brain regions.     

Time-course of malaoxon-induced alterations in brain regional inositol-1-phosphate levels in convulsing and nonconvulsing rats

The potential of a single dose of malaoxon (26.2 or 39.2 mg/kg i.p.) to produce convulsions and to increase cerebral levels of inositol-1-phosphate (Ins1P), an intermediate in phosphoinositide (PI) cycle, was followed for 1, 4, or 72 hr. The lower dose of malaoxon did not produce convulsions whereas the higher dose induced convulsions in 60% of the exposed rats. Malaoxon caused a dosedependent, at most 2-fold, increase in brain regional Ins1P levels in nonconvulsing rats as compared to controls. At the higher dose of malaoxon, in convulsing rats, the Ins1P-levels increased 4-fold above the control Ins1P-levels. In nonconvulsing rats, the Ins1P-levels reached their maximum 1–4 hr after the administration of malaoxon, whereas in convulsing rats the levels increased for 72 hr. The results suggest that PI-signalling is associated with convulsions produced by malaoxon.