An autoradiographic analysis of [125I]alpha-bungarotoxin binding in rat brain after chronic nicotine exposure

Chronic exposure to nicotine has been shown to increase binding to high affinity nicotinic cholinergic receptors in rat brain, but the effect of this treatment on the low affinity alpha7 nicotinic receptors has been less well characterized. Male Sprague-Dawley rats were treated with saline or nicotine (6 mg/kg/day, by osmotic minipump) for 14 days. Frozen brain sections were then prepared and processed for quantitative autoradiography using [(125)I]alpha-bungarotoxin to measure the effect of this treatment on low affinity nicotinic receptors. Nicotine exposure increased [(125)I]alpha-bungarotoxin binding in 26 of 52 brain regions analyzed; increases ranged from 10 to 70% over saline controls. Increases were seen in all areas of the brain, but were more prominent in forebrain areas, and especially in cerebral cortex. These data demonstrate that low affinity alpha7 nicotinic receptors are also up-regulated by chronic nicotine. This phenomenon may be relevant to the heavy use of tobacco products in diseases like schizophrenia, and needs to be considered in the design of pharmaceuticals directed at this receptor system.