Chronic menthol attenuates the effect of nicotine on body temperature in adolescent rats

Menthol is a commonly used additive in tobacco products. Smoking cessation may be more difficult for smokers of mentholated cigarettes, particularly adolescent smokers. Evidence indicates that menthol can influence neurotransmitter receptors and nicotine metabolism. We investigated the effects of chronic menthol using body temperature as a bioassay for the effects of acute nicotine in vivo. Male rats (34-36 days, adolescent; 53-58 days, young adult; 9-10 months, full adult) were injected with menthol (100 mg/kg) or vehicle once daily for 4 days. On day 5, animals were injected with nicotine (0.5 mg/kg) and body temperature was measured for the next 70 min. We found no effect of chronic menthol treatment or of age on baseline temperature. Nicotine quickly produced vasodilatory hypothermia in all animals. Chronic menthol treatment had significant effects only in adolescent rats, diminishing nicotine-induced hypothermia. Nicotine treatment was repeated on day 6 to test for tolerance. Equivalent tolerance was found in all ages, and the attenuating effect of menthol was still present and was still limited to adolescent rats. In adolescents, acute menthol injection (400 mg/kg) 30 min prior to nicotine also attenuated nicotine-induced hypothermia but with a smaller effect size. Also in adolescents, we found no effect of chronic or acute menthol on hypothermia induced by hydralazine, a peripherally acting vasodilator. These data demonstrate that menthol diminishes the influence of nicotine on body temperature in adolescents, suggesting a greater susceptibility of youthful physiology to menthol.