Chronic treatment with cholinesterase inhibitors increases alpha 2-adrenoceptors in rat brain.

The specific binding of [3H]clonidine to alpha 2-adrenoceptors on neural membranes isolated from various brain areas was determined with rats treated for 7-14 days with the cholinesterase inhibitors neostigmine, triorthocresyl phosphate (TOCP), diisopropylfluorophosphate (DFP) and paraoxon, or with vehicle. Treatment with all four inhibitors increased the number of clonidine binding sites in various brain areas. In those areas which demonstrated significant increases in [3H]clonidine binding, there was also a significant inhibition of acetylcholinesterase activity. The possibility is discussed that increases in brain alpha 2-adrenoceptors are related to the alterations in mood seen in individuals chronically exposed to organophosphorus cholinesterase inhibitors.