Cerebral Cortical Vasodilatation Mediated by Nicotinic Cholinergic Receptors: Effects of Old Age and of Chronic Nicotine Exposure

Abstract

Nicotinic acetylcholine receptors in the brain play a crucial role in the vasodilation in the cerebral cortex induced by basal forebrain cholinergic activation. Nicotinic receptors can be up-regulated or down-regulated in various conditions, e.g., up-regulation (increase in number) is found in smokers and in rodents exposed to chronic nicotine, while down-regulation (decrease in number) is found in elderly humans and in aged rats. We found in anesthetized rats that the increase in cortical cerebral blood flow induced by bolus intravenous nicotine injection was due to a vasodilation mediated by nitric oxide following activation of nicotinic receptors, probably of alpha4beta2-like subtype, both in the basal forebrain nuclei (Meynert nucleus) and in the cortex. This vasodilative response was reduced by long-term nicotine treatment and also in aged rats. Our results show that functional changes in nicotinic receptors are not always in the same direction as the changes in number; they highlight the importance of investigating not only the changes in receptor numbers but also those in their functional activity.