Effects of stress on circulating nicotine and cotinine levels and in vitro nicotine metabolism in the rat

The effects of physical and psychological stress on circulating nicotine levels and conversion of nicotine to cotinine were examined in the rat. Animals received one of three dosages of nicotine (0, 6, and 12 mg/kg) via miniosmotic pumps. On day 14 of drug infusion, animals from each drug condition were randomly assigned to one of three stress conditions (noise, rubber ligature, or no stress). After 2.5 h of stress exposure, animals were killed and plasma nicotine and cotinine were measured in vivo and hepatic conversion of nicotine to cotinine was determined in vitro. Stress lowered blood nicotine levels. However, this difference was statistically significant only among animals receiving 12 mg/kg per day nicotine. In contrast, stress had no consistent effect on either measure of conversion of nicotine to cotinine in rats. Taken together, these results suggest that stress lowers circulating nicotine levels. However, the mechanism by which this occurs remains unclear.