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 w ell as increases in brain [H-3]-nicotine binding and [I-125]-alpha-bun garotoxin (alpha-BTX) binding. Chronic corticosterone (CCS) treatment also produces tolerance to nicotine, but it does not change [H-3]-nico tine binding; decreases in alpha-BTX binding are observed, which sugge sts that tolerance to nicotine may be related to decreases in the numb er of this nicotinic receptor subtype. In the studies reported here, C 57BL/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 n icotine challenge on Y-maze crossing and rearing activities, heart rat e, and body temperature were measured. Both chronic nicotine and CCS t reatment resulted in tolerance to nicotine for all of the measures, an d some evidence for additivity was seen in the animals that were cotre ated with CCS and nicotine. Chronic nicotine infusion increased brain nicotine binding and CCS treatment reduced alpha-BTX binding. Decrease s in alpha-BTX binding were not detected in the cotreated animals. The latter finding argues that changes in alpha-BTX binding are not relia ble predictors of or a cause of tolerance to nicotine.