Correlations between acetylcholinesterase inhibition, acetylcholine levels and EEG changes during perfusion with neostigmine and N6-cyclopentyladenosine in rat brain.
Organophosphate poisoning can result in seizures and subsequent neuropathology. In order to improve treatment strategies in organophosphate intoxication, the relationship between acetylcholinesterase inhibition, extracellular levels of acetylcholine, and electroencephalogram (EEG) changes was investigated during local perfusion of the reversible acetylcholinesterase inhibitor neostigmine in the hippocampus and striatum of freely moving rats. Acetylcholinesterase activity and acetylcholine levels were measured by microdialysis, and EEG signals were recorded from an electrode placed near the microdialysis probe. A non-linear relationship between the acetylcholinesterase activity and the extracellular amount of acetylcholine was found, the latter being approximately three times higher in the striatum than in the hippocampus upon infusion with 10(-4) M neostigmine. Highly accumulated extracellular acetylcholine significantly correlated with significant relative power increases of the EEG-gamma2-band and a significant relative power decrease in the beta2-band. Co-infusion of the adenosine A1 agonist N6-cyclopentyladenosine partly prevented acetylcholine accumulation, rendered both powers towards control values, and abolished the acetylcholine-EEG correlation. In view of the latter relationship, it is concluded that prevention of acetylcholine accumulation as a concept for neuroprotection in case of organophosphate poisoning, is worth to be further investigated.
Joosen
Marloes J A
MJ
TNO Defence, Security and Safety, BU Biological and Chemical Protection, Department Diagnosis and Therapy, Rijswijk, The Netherlands. Marloes.joosen@tno.nl
van Helden
Herman P M
HP
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004569:Electroencephalography; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D017551:Microdialysis; D009388:Neostigmine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D058907:Adenosine A1 Receptor Agonists; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D009388:Neostigmine; C048599:N(6)-cyclopentyladenosine; D000110:Acetylcholinesterase; D000241:Adenosine; D000109:Acetylcholine