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Chronic alpha7 and alpha4-beta2 hippocampal nicotinic receptor blockade and systemic nicotine effects on memory function in rats



Chronic alpha7 and alpha4-beta2 hippocampal nicotinic receptor blockade and systemic nicotine effects on memory function in rats



Society for Neuroscience Abstracts 27(1): 207



Hippocampal nicotinic innervation is a critical substrate for working memory function. Both alpha4-beta2 and alpha7 nicotinic receptors are involved. We have found that acute ventral hippocampal infusion of the alpha4-beta2 nicotinic antagonist dihydro-beta-erythrodine (DHbE) and the alpha7 nicotinic antagonist methyllycaconitine (MLA) impair memory of Sprague-Dawley rats on the radial-arm maze in a dose-related manner. We have also determined the effects of chronic 4-week local infusion of DHbE or MLA into the ventral hippocampus of rats via slow delivery osmotic minipumps connected to infusion cannulae. Both DHbE and MLA chronic infusions into the ventral hippocampus caused significant choice accuracy deficits in the radial-arm maze. The memory impairment persisted for the duration of infusion and then improved after withdrawal of the chronic nicotinic antagonist. Systemic nicotine administration attenuated chronic hippocampal DHbE infusion-induced memory impairment more effectively than chronic hippocampal MLA infusion-induced memory impairment. Chronic local nicotinic blockade provides a forum in which to determine the reaction of other neural systems to the persistent underactivity of hippocampal nicotinic systems. This chronic nicotinic blockade procedure may provide a better model of the chronic decrease in nicotinic receptor number seen in Alzheimer's disease. Nicotinic involvement in the cognitive aspects of drug addiction and recovery can also be determined. Novel treatments mediated via nicotinic and related systems can be evaluated in the chronic local blockade model.

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