RESUMEN
Tobacco addiction has been largely attributed to nicotine, a component in tobacco leaves and smoke. However, extensive evidence suggests that some non-nicotine components of smoke should not be overlooked when considering tobacco dependence. Yet, their individual effect and synergistic effect on nicotine reinforcement remain poorly understood. The study herein focused on the role of non-nicotine constituents in promoting the effects of nicotine and their independent reinforcing effects. Denicotinized cigarettes were prepared by chemical extracting of cut tobacco, and the cigarette smoke extracts (CSE, used as a proxy for non-nicotine ingredients) were obtained by machine-smoking the cigarettes and DMSO extraction. The compositions of harmful components, nicotine, and other minor alkaloids in both cut tobacco and the CSE of experimental denicotinized cigarettes were examined by GC-MS, and compared with 3R4F reference cigarettes. individually and in synergy with nicotine were determined by conditioned place preference (CPP), dopamine (DA) level detection, the open field test (OFT), and the elevated plus maze (EPM). Finally, the potential enhancement mechanism of non-nicotinic constituents was investigated by nicotine metabolism and monoamine oxidase A (MAOA) activity inhibition in the striatum of mice and human recombinant MAOA. Thenicotine content in smoke from the experimental denicotinized cigarettes (under ISO machine-smoking conditions) was reduced by 95.1% and retained most minor alkaloids, relative to the 3R4F reference cigarettes. It was found that non-nicotine constituents increased acute locomotor activities. This was especially pronounced for DA levels in NAc and CPP scores, decreased the time in center zone. There were no differences in these metrics with DNC group when compared to the NS group. Non-nicotine constituents alone did not show reinforcing effects in CPP or striatum DA levels in mice. However, in the presence of nicotine, non-nicotine constituents further increased the reinforcing effects. Furthermore, non-nicotine constituents may enhance nicotine's reinforcing effects by inhibiting striatum MAOA activity rather than affecting nicotine metabolism or total striatum DA content in mice. These findings expand our knowledge of the effect on smoking reinforcement of non-nicotine constituents found in tobacco products.
RESUMEN
RATIONALE: Individuals with attention deficit hyperactivity disorder (ADHD) start smoking earlier, are more likely to progress to nicotine dependence, and have a more difficult time quitting smoking compared to their non-ADHD peers. Little is known about the underlying behavioral mechanisms associated with this increased risk, particularly at the adolescent stage. OBJECTIVE: This study aimed to assess the effects of overnight nicotine abstinence and smoking reinstatement on subjective withdrawal states in adolescent smokers with and without ADHD. METHODS: Adolescent daily smokers (27 with ADHD and 17 without ADHD) completed three experimental sessions: (1) a placebo patch followed by smoking a nicotine cigarette, (2) placebo patch followed by smoking a nicotine-free cigarette, and (3) nicotine patch followed by smoking a nicotine-free cigarette. Subjects abstained overnight before each session, and patches were administered 45 min before smoking. The primary outcome measure was a smoking withdrawal symptom questionnaire. RESULTS: ADHD smokers experienced greater difficulty concentrating and impatience/restlessness during abstinence than non-ADHD smokers. Smoking a cigarette improved abstinence-induced difficulty concentrating and restlessness, regardless of its nicotine content, and regardless of whether transdermal nicotine was received or not. CONCLUSIONS: Thus, sensorimotor aspects of smoking, rather than nicotine itself, appeared to relieve withdrawal. Although ADHD smokers report greater withdrawal symptoms than non-ADHD smokers, they responded strongly to the sensorimotor aspects of smoking during withdrawal. These findings suggest that even lighter, adolescent smokers with ADHD are vulnerable to smoking progression through altered smoking abstinence and withdrawal relief processes.