Protective effects of mecamylamine and atropine against α(4)β(2) nicotinic receptor expression and functional toxicity in paraoxon-treated rats

Environ Toxicol Pharmacol. 2008 Sep;26(2):247-54. doi: 10.1016/j.etap.2008.05.003. Epub 2008 May 31.

Abstract

Chronic and acute exposure to organophosphate pesticides or related nerve agents may lead to persistent neurological and neurobehavioral effects, which cannot be explained by acetylcholinesterase (AChE) inhibition alone. In the present study, the effects of mecamylamine (2mg/kg), or atropine (10mg/kg) alone, or in combination, on the expression of nicotinic acetylcholine receptors (nAChRs) subunits, functional signs of toxicity and lethality in paraoxon-treated rats were investigated. Surviving animals were sacrificed after 48h of paraoxon administration. Paraoxon, at dosage of 1× LD50, significantly reduced expression of α(4) and β(2) nAChR subunits mRNA and protein in rat brain homogenates. Mecamylamine, efficiently prevented reduction of the α(4) and β(2) nAChR mRNA and protein in paraoxon exposed rat brains, but atropine was not efficient. Concurrent treatment with mecamylamine and atropine restored nAChRs mRNA and protein level and prevented lethality and severe involuntary movements induced by paraoxon. Nicotinic receptors antagonists may be included in the cocktail of therapeutic agents targeting the various mechanisms for neuronal injury by organophosphates.