Rationale: Nicotine, a dominant alkaloid found in tobacco, is responsible for physical dependence, as well as addiction to cigarette smoking; consequently, smoking cessation is a very difficult process. Hepatic cytochrome P-450 2A6 (CYP2A6) is involved in the 70-80 % of the initial metabolism of nicotine and its co-metabolites. As this metabolism is slowed by inhibitors of CYP2A6, this kind of enzymatic inhibition has been proposed as a novel target for smoking cessation.
Objectives: Nicotine administered alone improved memory acquisition and consolidation as well as exerted antidepressive activity in animal models. These effects persist for 24 h. However, they are completely extinguished 48 h after administration.
Methods: To investigate if the coumarins prolong the behavioral effects of nicotine, the forced swimming test (FST)-animal models of depression, and passive avoidance (PA) test-memory and learning paradigm were used.
Results: This study revealed that three CYP2A6 inhibitors: two furanocoumarins, xanthotoxin (15 mg/kg) and bergapten (25 mg/kg), and the simple coumarin umbelliferone (25 mg/kg), prolonged the antidepressive and procognitive effects of nicotine.
Conclusions: These natural products may offer a new approach to the treatment of nicotinism as antidepressant and memory improvement actions are one of the main factors of nicotine dependence.
Keywords: Coumarins; Depression; Memory; Mice; Nicotine.