Neurotransmitter Changes in Guinea‐Pig Brain Regions Following Soman Intoxication

Abstract

The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman (31.2 micrograms/kg s.c.) on guinea-pig brain AChE, transmitter, and metabolite levels were investigated. Concentrations of acetylcholine (ACh) and choline (Ch), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites, and six putative amino acid transmitters were determined concurrently in six brain regions. The brain AChE activity was maximally inhibited by 90%. The ACh content was elevated in most brain areas by 15 min, remaining at this level throughout the study. This increase reached statistical significance in the cortex, hippocampus, and striatum. The Ch level was significantly elevated in most areas by 60-120 min. In all regions, levels of NA were reduced, and levels of DA were maintained, but those of its metabolites increased. 5-HT levels were unchanged, but those of its metabolites showed a small increase. Changes in levels of amino acids were restricted to those areas where ACh levels were significantly raised: Aspartate levels fell, whereas gamma-aminobutyric acid levels rose. These findings are consistent with an initial increase in ACh content, resulting in secondary changes in DA and 5-HT turnover and release of NA and excitatory and inhibitory amino acid transmitters. This study can be used as a basis to investigate the effect of toxic agents and their treatments on the different transmitter systems.

Pretreatment of Guinea Pigs with Galantamine Prevents Immediate and Delayed Effects of Soman on Inhibitory Synaptic Transmission in the Hippocampus

“…In hippocampal microdialysates, levels of the inhibitory neurotransmitter GABA have been shown to decrease in guinea pigs at 1 to 2 h after exposure to soman (Fosbraey et al, 1990). On the other hand, levels of GABA have been found to be significantly increased in hippocampal tissue obtained from rats at 80 min after the onset of soman-induced seizures (Shih and McDonough, 1997).…”

Central Mechanisms of Seizures and Lethality Following Anticholinesterase Pesticide Exposure

“…Levels of noradrenaline were reduced by soman in guinea pig cortex, hippocampus, and striatum (Fosbraey et al, 1990). Noradrenaline levels specifically declined by up to 70% in forebrain of somantreated convulsive rats.…”

“…Some data suggest that decreased striatal noradrenaline level may play a role in soman-induced neurotoxicity and seizures (Buccafusco and Aronstam, 1987;Coudray-Lucas et al, 1987;el-Etri et al, 1992;Fosbraey et al, 1990;Shih and McDonough, 1997). Levels of noradrenaline were reduced by soman in guinea pig cortex, hippocampus, and striatum (Fosbraey et al, 1990).…”

The effects of repeated low-dose sarin exposure☆

“…Upon exposure to CWNAs, increases in total brain ACh levels are immediate (Shih, 1982;Fosbraey et al, 1990Fosbraey et al, , 1991Shih et al, 1993;Shih and McDonough, 1997), but return to baseline levels extracellularly within 90 minutes of seizure onset (Lallement et al, 1992). An increase in dopamine metabolites, i.e., 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic acid (HVA), is evident approximately 10 minutes after seizure onset with increases in HVA continuing for up to 80 minutes after seizure onset McDonough and Shih, 1997).…”