Subchronic treatment of rats with nicotine: effects on tolerance and on [3H]acetylcholine and [3H]nicotine binding in the brain.

The effects of subchronic nicotine treatment on the development of tolerance and on two nicotinic ligand binding sites were investigated. After subcutaneous injection of nicotine (0.45 mg nicotine base/kg) or saline twice a day for 14 days the body weight of rats was significantly lower than that of control animals. A significant tolerance to the acute effects of nicotine on locomotor activity and body temperature was observed after the treatment period. Nicotine treatment also resulted in a significant increase in [3H]acetylcholine (3H-ACh) binding in the midbrain (48.3% increase in comparison with controls) and hippocampus (38.3% increase), whereas the binding of [3H]nicotine (3H-NIC) was unaffected in all brain areas investigated. These results indicate that subchronic s.c. injections of nicotine can differentially affect the binding of two different nicotinic ligands in the brain. It is also concluded that the development of tolerance to the acute effects of nicotine on locomotor activity and temperature is not directly dependent upon changes in binding of [3H]nicotine to the brain.