Changes in sensitivity to nicotine and brain nicotinic receptors following chronic nicotine and corticosterone treatments in mice

Chronic nicotine treatment often results in tolerance to nicotine as well as increases in brain [³H]nicotine binding and [¹²⁵I]-α-bungarotoxin (α-BTX) binding. Chronic corticosterone (CCS) treatment also produces tolerance to nicotine, but it does not change [³H]-nicotine binding; decreases in α-BTX binding are observed, which suggests that tolerance to nicotine may be related to decreases in the number of this nicotinic receptor subtype. In the studies reported here, C57BL/6 mice were implanted subcutaneously with cholesterol or 60% CCS/40% cholesterol-containing pellets and were infused continuously with saline (control) or nicotine for a total of 9 days. Effects of acute nicotine challenge on Y-maze crossing and rearing activities, heart rate, and body temperature were measured. Both chronic nicotine and CCS treatment resulted in tolerance to nicotine for all of the measures, and some evidence for additivity was seen in the animals that were cotreated with CCS and nicotine. Chronic nicotine infusion increased brain nicotine binding and CCS treatment reduced α-BTX binding. Decreases in α- BTX binding were not detected in the cotreated animals. The latter finding argues that changes in α-BTX binding are not reliable predictors of or a cause of tolerance to nicotine.