Phosalone-Induced Changes in Regional Cholinesterase Activities in Rat Brain during Behavioral Tolerance
Organophosphate pesticides exert their toxic effects by cholinesterase
inhibition and the consequent prolongation of the undesirable effects of
accumulation of acetylcholine. The signs of toxicity include tremors,
convulsions, lachrymation, defecation etc. However, sustained cholinesterase inhibition through sustained administration of organophosphates would lead to the gradual disappearance of the initial signs of toxicity over time, termed behavioral tolerance. The present study was undertaken to examine the activity levels of cholinesterases in different regions of rat brain during the development of behavioral tolerance to the organophosphate phosalone. Male albino rats were given a daily oral dose of phosalone (41.35 mg, equivalent to ¼ of LD50) every day for 15 days and the activities of acetylcholinesterase (AChE) butyrylcholinesterase (BuChE) and pseudocholinesterase (PChE) were estimated at intervals at 1, 3, 9 and 15 days of treatment. All the cholinesterases were inhibited, and this inhibition was found to vary among different brain regions at different times. Greater inhibition of AChE and BuChE activities was observed at 9 days, while for PChE it was recorded at 3 days. Recovery trend to normalcy was observed earlier in PChE compared to AChE and BuChE. The signs and symptoms of pesticide toxicity were mainly cholinergic. Inhibition of cholinesterases was well correlated with the appearance and severity of signs and symptoms. Tremors and convulsions in particular were more after 9 days. After 9 days, decline followed by disappearance of majority of the signs and symptoms was
noticed while reduction in cholinesterase activities still continued, indicating
the development of behavioral tolerance to phosalone. Among the brain
regions, striatum recorded a greater decrease in cholinesterase activity.
Earlier recovery of pseudocholinesterase activity seems to be an interesting
phenomenon in regulating homeostasis of cholinesterases and in the
development of symptomatic tolerance of phosalone.
Key words: Phosalone, Cholinesterases, Rat brain, Behavioral
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