脑N受体α_7亚型同源性上行性调节的药理学特征

目的　研究脑N受体α7亚型同源性上行性调节的药理学特征。方法　在体外培养的海马神经元中加入不同浓度的胆碱、烟碱及甲基牛扁碱 ,孵育 7d ,用γ计数器检测[12 5I]α 银环蛇毒素结合位点的变化情况。结果　胆碱(0 0 0 1～ 1μmol·L-1) ,烟碱 (>10 μmol·L-1)以及甲基牛扁碱 (>10 μmol·L-1)长期作用后 ,都可以增加 [12 5I]α 银环蛇毒素的结合量 (P <0 0 5 ) ,但对解离常数 (Kd)无影响 (P >0 0 5 )。结论　在一定浓度范围内 ,胆碱、烟碱和甲基牛扁碱长期作用可使海马神经元上的N受体α7亚型数目上调 ,且胆碱与烟碱上调α7受体的药理学特征不同。     

Increased susceptibility to adult paraoxon exposure in mice neonatally exposed to nicotine.

Low-dose exposure of neonatal mice to nicotine has earlier been shown to induce an altered behavioral response to nicotine in adulthood. Organophosphorus insecticides are known to affect the cholinergic system by inhibition of acetylcholinesterase. This study was undertaken to investigate whether neonatal exposure to nicotine makes mice more susceptible to a known cholinergic agent. Neonatal, 10-day-old, male mice were exposed to nicotine-base (33 microg/kg body weight) or saline s.c. twice daily on five consecutive days. At 5 months of age the animals were exposed to paraoxon (0.17 or 0.25 mg/kg body weight [29% and 37% inhibition of cholinesterase, respectively]) or saline sc every second day for 7 days. Before the first paraoxon injection, the animals were observed for spontaneous motor behavior. The spontaneous motor behavior test did not reveal any differences in behavior between the treatment groups. Immediately after the spontaneous behavior test, the animals received the first injection of paraoxon and were observed for acute effects of paraoxon on spontaneous motor behavior. The acute response to paraoxon in the spontaneous motor behavior test was a decreased level of activity in mice neonatally exposed to nicotine. Control animals showed no change in activity. Two months after the paraoxon treatment, the animals were again tested for spontaneous motor behavior. Animals neonatally exposed to nicotine and exposed to paraoxon as adults showed a deranged spontaneous motor behavior, including hyperactivity and lack of habituation.     

Combined Ecological Momentary Assessment and Global Positioning System Tracking to Assess Smoking Behavior: A Proof of Concept Study

Objective: Ecological momentary assessment (EMA) methods have provided a rich assessment of the contextual factors associated with a wide range of behaviors including alcohol use, eating, physical activity, and smoking. Despite this rich database, this information has not been linked to specific locations in space. Such location information, which can now be easily acquired from global positioning system (GPS) tracking devices, could provide unique information regarding the space-time distribution of behaviors and new insights into their determinants. In a proof of concept study, we assessed the acceptability and feasibility of acquiring and combining EMA and GPS data from adult smokers with attention deficit hyperactivity disorder (ADHD). Methods: Participants were adults with ADHD who were enrolled in a larger EMA study on smoking and psychiatric symptoms. Among those enrolled in the latter study who were approached to participate (N = 11), 10 consented, provided daily EMA entries, and carried a GPS device with them during a 7-day assessment period to assess aspects of their smoking behavior. Results: The majority of those eligible to participate were willing to carry a GPS device and signed the consent (10 out of 11, 91%). Of the 10 who consented, 7 participants provided EMA entries and carried the GPS device with them daily for at least 70% of the sampling period. Data are presented on the spatial distribution of smoking episodes and ADHD symptoms on a subset of the sample to demonstrate applications of GPS data. Conclusions: We conclude by discussing how EMA and GPS might be used to study the ecology of smoking and make recommendations for future research and analysis.     

Immunomodulation of dendritic cells differentiated in the presence of nicotine with lipopolysaccharide from Porphyromonas gingivalis

Tobacco smoking is a significant risk factor for periodontal diseases. Nicotine, one of the most studied constituents in cigarette smoke, is thought to modify immune responses. Dendritic cells (DCs), which are key mediators between innate and adaptive immunity, stimulate naive T cells to differentiate to effector T‐cell subsets that may be actively involved in the immunopathogenesis of periodontal diseases. In this study, we evaluated the effects of nicotine and lipopolysaccharide (LPS) from Porphyromonas gingivalis, alone and in combination, on the functions of human monocyte‐derived DCs to elucidate the mechanism of tissue destruction of smoking‐associated periodontal diseases. P. gingivalis LPS‐stimulated DCs differentiated with nicotine (NiDCs) induced lower T‐cell proliferation and human leukocyte antigen (HLA)‐DR expression, but elevated expression of programmed cell death ligand 1. Additionally, NiDCs impaired interferon‐γ production but maintained interleukin (IL)‐5 and IL‐10 production in co‐cultured T cells. Furthermore, NiDCs produced lower levels of proinflammatory cytokines compared with DCs differentiated in the absence of nicotine. Interestingly, NiDCs preferentially produced the T helper 2 (Th2)‐type chemokines macrophage chemotactic protein‐1 and macrophage‐derived chemokine. These results suggest that the presence of nicotine during differentiation of DCs modulates the immunoregulatory functions of P. gingivalis LPS‐stimulated DCs.     

Associations Between Initial Subjective Experiences with Tobacco and Self-Reported Recent Use in Young Adulthood

Background: Youth tobacco use behaviors are predictive of patterns in adulthood and effect long-term health outcomes. Yet, few studies have examined the effect of initial subjective experiences (ISEs) during first tobacco use, which has been found to be an indicator of individuals. sensitivity to nicotine and vulnerability to dependence. Objective: The present study aimed to determine the prevalence of ISEs across a variety of tobacco products, evaluate the factor structure of ISEs by first tobacco product used, and examine the relationship between ISEs and recent (30-day) use of tobacco products across time, using a university sample. Methods: Exploratory factor analyses were conducted to identify latent factors present with respect to items measuring ISEs with tobacco, separately by tobacco product (e.g. cigarettes, cigars, hookah, e-cigarettes). Factor scores for positive and negative ISEs were calculated. Multiple logistic regression analyses were conducted to examine associations between ISEs and recent use of each tobacco product, adjusted for age at first use, sex, race/ethnicity, and cohort. Results: ISEs differ by the first tobacco product used. Associations between factor scores for positive and negative ISEs and recent use were found across a variety of tobacco products. Overall, positive ISEs were more strongly associated with recent use, relative to negative ISEs. Conclusions: Further research is needed to identify genetic and biological pathways and social contexts influencing initial subjective experiences with tobacco use, in efforts to delay the initiation for tobacco use and reduce risk for continued use among young adults.