Abstract
RationaleNicotine, 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.ObjectivesNicotine 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.MethodsTo 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.ResultsThis 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.ConclusionsThese 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.
Highlights
Nicotine, the main component of tobacco smoke, influences the mood and emotional tension, as well as contributes to development of physical and mental dependence
Our present studies revealed that xanthotoxin, bergapten, and umbelliferone exerted procognitive effects in passive avoidance (PA) test; whereas, they did not influence immobility time in the forced swimming test (FST) measured 24 h after drug injections
For the first time, it was revealed that the two furanocoumarins, xanthotoxin, and bergapten, as well as the simple coumarin, umbelliferone, prolonged the antidepressive, as well as the procognitive effects of nicotine, and these results are not modulated by the influence of these compounds on locomotor activity
Summary
The main component of tobacco smoke, influences the mood and emotional tension, as well as contributes to development of physical and mental dependence. It is well documented that nicotine exerts cognitive effects (Herman et al 2010; Levin 2002; Levin et al 2009), analgesia (Marubio et al 1999), and an influence on anxiety- (File et al 2000) or depression-like behaviors (Hayase 2011). The effects of nicotine have been extensively investigated in humans and in animals and several cell systems (Biala et al 2014; Budzynska et al 2012b; Dani and De Biasi 2001; Kruk-Slomka et al 2012; Malin 2001). Plants containing coumarins are used in traditional medicine all over the world for their antiproliferative, anticonvulsant, anxiolytic, and procognitive effects (Abed et al 2001; Budzynska et al 2012a; Garcia-Argaez et al 2000; Kawaii et al 2001; Luszczki et al 2007)
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