Nicotine addiction is a concern worldwide. Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects. However, no effective therapeutic treatment has been established. Nicotine addiction is reinforced by environments or habits. We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction. We utilized the conditioned place preference to establish nicotine-associated behavioural preferences (NABP) in rats. Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex (mPFC) was activated and contributed to NABP. Chemogenetic manipulation of µ-opioid receptor positive (MOR⁺) neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell (NAcShell) modulated the NABP. Electrophysiological recording confirmed that the MOR⁺ neurons directly regulate the mPFC-NAcShell circuit via GABA_A receptors. Thus, the MOR⁺ neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell, which may provide new insight for the development of effective therapeutic strategies.
Animals ; Nucleus Accumbens/drug effects* ; Prefrontal Cortex/drug effects* ; Nicotine/pharmacology* ; Receptors, Opioid, mu/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Tobacco Use Disorder/metabolism* ; Neurons/drug effects* ; Neural Pathways/drug effects*

OBJECTIVE: Cigarette smoking is associated with a variety of health problems including cardiovascular, pulmonary, neoplasms, endocrinopathies including diabetes, the metabolic syndrome, and chronic inflammation. Adiponectin is an adipocyte-derived plasma protein that is closely associated with insulin sensitivity and the metabolic syndrome. The aim of this study was to evaluate the changes of plasma adiponectin levels after smoking cessation. METHODS: Thirty seven smokers that wanted to stop smoking without any nicotine replacement therapy or medication were recruited for this study. Fifteen smokers succeeded in stopping smoking (validated by urine cotinine levels < or =50 ng/mL) and 22 smokers failed. Therefore, only the 15 that succeeded were included in the analysis. The plasma adiponectin levels were determined using a commercially available enzyme-linked immunosorbent assay. RESULTS: The mean age of the successful 15 was 35+/-9.3 years old. They were all males. The daily smoking habit was a mean of 13.5+/-5.4 cigarettes per day. The mean Nicotine Dependence Syndrome Scale (NDSS) and Fagerstrom Test for Nicotine Dependence (FTND) scores were 55.6+/-9.6 and 2.9+/-1.9. During the study period of three months, the mean body mass index (BMI), body fat mass (BFM), waist-hip ratio (WHR) and body weight increased by 1.1 kg/m2, 3.0%, 0.02%, and 2.9 kg, respectively. The baseline mean adiponectin level in the subjects was 11.9+/-5.2 mg/L. The mean adiponectin levels measured at one and three months were 16.0+/-5.1 mg/L and 14.7+/-4.5 mg/L respectively. The mean plasma adiponectin levels of the successful group was significantly increased after four weeks when compared to the baseline (z=-2.401, p=0.016). However, the decrease in plasma adiponectin levels at one and three months was not statistically significant. CONCLUSION: Even though the decrease over the next two months was not significant, these findings, the increase of plasma level of adiponectin after smoking cessation, provide preliminary data for future research on the possible mechanisms associated with smoking cessation and changes in body metabolism.
Adiponectin* ; Adipose Tissue ; Body Mass Index ; Body Weight ; Cotinine ; Enzyme-Linked Immunosorbent Assay ; Ghrelin ; Humans ; Inflammation ; Insulin Resistance ; Leptin ; Male ; Metabolism ; Nicotine ; Plasma* ; Smoke* ; Smoking Cessation* ; Smoking* ; Tobacco ; Tobacco Products ; Tobacco Use Disorder ; Waist-Hip Ratio

Nicotine is the main component for smoking addiction. It is widely believed that nicotine dependence is heritable. Many studies are committed to study the effects of specific gene polymorphisms connect with nicotine dependence. Release of dopamine has been considered the most important channel for nicotine dependence. This paper provides a review for recent advance in studies on dopamine system related genetic polymorphisms associated with nicotine dependence.
Animals ; Dopamine ; metabolism ; Humans ; Nicotine ; metabolism ; Polymorphism, Genetic ; Tobacco Use Disorder ; genetics ; metabolism

Alleles ; Animals ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP2A6 ; Humans ; Mixed Function Oxygenases ; genetics ; metabolism ; Nicotine ; metabolism ; Polymorphism, Genetic ; Tobacco Use Disorder ; metabolism