Selective breeding for differences in cholinergic function: pre- and postsynaptic mechanisms involved in sensitivity to the anticholinesterase, DFP.
To determine the contribution of presynaptic cholinergic mechanisms to the increased sensitivity of a genetically selected line of Sprague-Dawley rats (Flinders S-line) to the anticholinesterase, diisopropyl fluorophosphate (DFP), rats were sacrificed by focused microwave irradiation of the head 1 min after a pulse injection of deuterium-labeled choline into the tail vein. The S-line rats exhibited higher concentrations of labeled acetylcholine (ACh) in the cortex than the rats bred for resistance to DFP (Flinders R-line). To determine the contribution of postsynaptic cholinergic mechanisms the concentration of brain muscarinic ACh receptors (mAChR) was determined. The S-line rats exhibited higher concentrations of striatal and hippocampal mAChR than the R-line rats. Thus, both pre- and postsynaptic cholinergic mechanisms may contribute to the increased sensitivity to DFP but their relative importance varies with brain region: increased ACh synthesis in the cortex and increased concentrations of mAChR in the striatum and hippocampus.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007531:Isoflurophate / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics*; D011976:Receptors, Muscarinic / Q000378:metabolism; D012737:Sex Factors; D013045:Species Specificity; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014018:Tissue Distribution
D011976:Receptors, Muscarinic; D007531:Isoflurophate; D002794:Choline; D000109:Acetylcholine