A Guinea Pig Hippocampal Slice Model of Organophosphate-Induced Seizure Activity

Abstract

Extracellular recording techniques have been used in the guinea pig hippocampal slice preparation to investigate the electrophysiological actions of the organophosphate (OP) anticholinesterase soman. When applied at a concentration of 100 nM, soman induced epileptiform activity in the CA1 region in approximately 75% of slices. This effect was mimicked by the anticholinesterases paraoxon (1 and 3 M), physostigmine (30 M), and neostigmine (30 M), thus providing indirect evidence that the epileptiform response was mediated by elevated acetylcholine levels. Soman-induced bursting was inhibited by the muscarinic receptor antagonists atropine (concentrations tested, 0

Nicotinic Antagonists in the Treatment of Nerve Agent Intoxication

“…Although there is evidence that dysfunction of brain nAChRs may have a role in the pathogenesis of certain types of human epilepsy, 3 evidence for anticonvulsant efficacy of centrally active nAChR antagonists in animal models of OP intoxication is lacking. 4,5 However, our understanding of the pharmacology and function of brain nAChRs is still sketchy and it is conceivable that nAChR antagonists may be developed in the future that could be useful in the treatment of seizures associated with severe OP intoxication. At present the agent used to control nerve-agent-induced seizures is diazepam, its efficacy having been clearly established in numerous animal studies (see, for example, Ref.…”

Effect of Acute Soman Exposure on GABAA Receptors in Rat Hippocampal Slices and Cultured Hippocampal Neurons

“…Previous studys indicate that most OP nerve agentinduced events that are secondary to AChE inhibition Harrison et al 2004). However, findings from this study suggest that it is unlikely that soman-induced GABA A receptor internalization is due to the same mechanism, because (1) the concentration of soman required to inhibit GABA neurotransmission and induce GABA A receptor endocytosis is much higher than that required to inhibit AChE activity in cultured neurons (Sawyer et al 1992); (2) another potent and deadly nerve agent, VX, at high concentrations, induced only moderate GABA A receptor endocytosis in cultured rat hippocampal neurons; (3) physostigmine, at concentrations that completely inhibit AChE activity (Hallak and Giacobini 1986), did not inhibit GABA neurotransmission in acute rat Fig.…”

Rapid Decontamination of Chemical Warfare Agents from the Skin

“…Guinea pigs have been evaluated for skin damage from burns and are often used as a wound-healing model for sulfur mustard (Ramos et al, 2008), as well as for skin irritation to toxic industrial chemicals (TIC) (Weaver et al, 2003;Kennedy, 2007). Guinea pigs have also been used to study absorption of CWAs through the skin (Wormser et al, 2002;Dalton et al, 2006) and uptake of radioactive sulfur mustard through the skin (Logan et al, 1999), as well as an animal model for evaluating pretreatment regimens to protect against CWAs (Wetherell et al, 2006) and for assessing ChE activity responses (Haigh et al, 2005) to GD exposure and OP-induced seizure (Harrison et al, 2004).…”