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Selective breeding for differences in cholinergic function: pre- and postsynaptic mechanisms involved in sensitivity
Abstract:
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.
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