Stress may enhance nicotine effects on periodontal tissues. An in vivo study in rats

OBJECTIVES AND BACKGROUND: Diabetes mellitus and smoking have been described as important risk factors that may affect the initiation and progression of periodontitis. Recent studies have pointed to potentially periodontal risk indicators, which include stress. The present study investigated the effects of stress associated with nicotine administration on periodontal breakdown resulting from ligature-induced periodontitis in rats. METHODS: Twenty adult male Wistar rats were used. After anesthesia, both mandibular first molars received a cotton ligature in the dento-gingival area. The animals were randomly assigned to one of the following experimental groups: A - saline solution, B - 0.73 mg of nicotine/kg/d (intraperitoneal), C - stress (immobilization - 2 h/d/40 d) associated with an intraperitoneal administration of saline solution, and D - stress (immobilization - 2 h/d/40 d) associated with an intraperitoneal injection of 0.73 mg of nicotine/kg/d. Forty days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. RESULTS: Intergroup analysis (ANOVA) revealed a greater bone loss (P < 0.05) in the animals of group D compared with the animals from groups A, B and C. In addition, the data revealed a significant effect of nicotine (group B) compared with groups A and C (P < 0.05), and no difference between groups A and C (P > 0.05). CONCLUSION: Within the limits of the present study, although stress did not affect periodontitis by itself, it significantly enhanced the effects of nicotine on the periodontal tissues.     

Involvement of human heat shock protein 90 alpha in nicotine-induced apoptosis

There have been conflicting reports of the apoptotic effects of nicotine on human cells and those studies reporting nicotine-induced apoptosis have not unequivocally clarified the molecular mechanisms underlying the effect. However, we found here that human RSa cells, established from embryonic fibroblastic cells doubly infected with Rous sarcoma virus and Simian virus 40, underwent apoptosis when cultured with medium containing 0.06-0.6 microM nicotine. The apoptosis was assessed by cellular DNA fragmentation and caspase-3 protease activation. Viability of RSa cells was reduced by nicotine treatment, as analyzed by MTT assay and the reduction was lessened by combination treatment with a caspase-3 inhibitor, acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspart-1-al (Ac-DEVD-CHO). Levels of expression of heat shock protein 90 alpha (Hsp90 alpha) were found to be increased 20 min after the nicotine treatment, as analyzed by polymerase chain reaction-based mRNA differential display after Northern blotting analysis of mRNA amounts. Cellular contents of Hsp90 alpha were furthermore increased in the nicotine-treated RSa cells, as quantitated by Western immunoblot analysis. By contrast, in RSa cells treated with nicotine in combination with geldanamycin (GA), an inhibitor of Hsp90 alpha function, DNA fragmentation was not detected and caspase-3 protease activity levels were the same as those of mock-treated cells. Nicotine-induced caspase-3 activation and Hsp90 alpha expression, as well as suppression of the induction by GA, were also observed in a xeroderma pigmentosum patient-derived cell line, XP2OS cells. Thus, it was suggested that nicotine induces apoptosis, possibly via Hsp90 alpha expression, in human cells tested.     

Nicotine alters striatal glutamate function and decreases the apomorphine-induced contralateral rotations in 6-OHDA-lesioned rats

The overall goal of this study was to determine the effects of subchronic nicotine (0.4 mg/kg) treatment for 7 or 14 days on striatal glutamate function in both na?ve and in 6-hydroxydopamine (6-OHDA)-treated rats in which the nigrostriatal dopamine pathway was lesioned. In lesioned animals, the effect of nicotine on apomorphine-induced contralateral rotations was also assessed. In na?ve rats, once daily nicotine administration for 7 or 14 days resulted in a decrease and then an increase, respectively, in the basal extracellular level of striatal glutamate compared to the saline-treated group. Ultrastructurally, 14-day treatment with nicotine resulted in an increase in the density of striatal glutamate immunolabeling within nerve terminals making an asymmetrical synaptic contact compared to the saline-treated group. In 6-OHDA-lesioned animals, coadministration of nicotine with apomorphine or nicotine alone for 7 days resulted in an increase in the density of nerve terminal glutamate immunolabeling, compared to the apomorphine- or saline-treated groups. However, coadministration of nicotine with apomorphine for 14 days resulted in a decrease in the density of nerve terminal glutamate immunolabeling compared to the nicotine-treated group. Following subchronic treatment of 6-OHDA-lesioned rats with apomorphine for 7 or 14 days, there was an increase in the number of apomorphine-induced contralateral rotations compared to the saline treated group. There was a decrease in the number of apomorphine-induced contralateral rotations in the group coadministered nicotine with apomorphine for 7 or 14 days compared to the apomorphine treated group. The data suggests that in this 6-OHDA lesion model of Parkinson's disease, treatment with nicotine may be useful in counteracting the increased behavioral effect (i.e., contralateral rotations) observed after treatment with a dopamine agonist, such as apomorphine.     

安非他酮缓释片戒除尼古丁依赖的多中心随机双盲对照试验

目的:评价国产安非他酮缓释片戒除尼古丁依赖的有效性及安全性。方法:多中心、随机、双盲、安慰剂平行对照研究。共入组自愿戒烟者143例,安非他酮组72例与安慰剂组71例。受试者分别口服安非他酮缓释片150～300 mg·d-1或安慰剂,疗程4 wk,观察12 wk。结果:治疗后4,12 wk安非他酮组戒烟率分别为39％,31％,高于安慰剂组(13％,9％),差异有非常显著意义(P<0．01);治疗后1 wk起安非他酮组吸烟量的减少值均大于安慰剂组,差异有非常显著意义(P<0．01)。安非他酮常见不良反应为注意力不集中、乏力、腹部不适等,其发生率高于安慰剂组,差异有显著意义(P<0．05),2组均未发生严重不良反应。结论:国产安非他酮缓释片是一种安全、有一定疗效的戒除尼古丁依赖(烟瘾)的药物。     

Modulation of the discriminative stimulus properties of (−)-nicotine by diazepam and ethanol

The effect of different ligands for the GABA-BZD receptor and the NMDA receptor were studied in rats trained to discriminate (?)-nicotine (1.9 μmol/kg) from saline in a standard two-bar operant conditioning paradigm with food reinforcement. MK-801 (0.03–0.3 μmol/kg), flumazenil (10–30 μmol/kg), and Ro 15–4513 (3–10 μmol/kg) did not generalize to (?)-nicotine on nicotine-trained rats, and when tested as antagonists they did not block the nicotine cue. Diazepam (3–10 μmol/kg) and ethanol (11–22 mmol/kg) did not have any effect by themselves, but they significantly attenuated the nicotine cue by 53 and 65%, respectively, without affecting the response rates of the animals. Pre-treatment with flumazenil (30 μmol/kg) reversed the effect of diazepam but it did not reverse the effect of ethanol on the discriminative stimulus properties of (?)-nicotine. The effect of ethanol was not blocked by Ro 15–4513 (10 μmol/kg). These data indicate that diazepam and ethanol modulate the expression of the nicotine cue and that the effect of diazepam is mediated via a benzodiazepine receptor mechanism. © Wiley-Liss, Inc.     

Neuronal nicotinic acetylcholine receptor expression and function on nonneuronal cells

Of the thousands of proven carcinogens and toxic agents contained within a cigarette, nicotine, while being the addictive agent, is often viewed as the least harmful of these compounds. Nicotine is a lipophilic molecule whose effects on neuronal nicotinic acetylcholine receptors (nAChR) have been primarily focused on its physiologic impact within the confines of the brain and peripheral nervous system. However, recently, many studies have found neuronal nAChRs to be expressed on many different nonneuronal cell types throughout the body, where increasing evidence suggests they have important roles in determining the consequences of nicotine use on multiple organs systems and diseases as diverse as ulcerative colitis, chronic pulmonary obstructive disease, and diabetes, as well as the neurologic disorders of Parkinson's and Alzheimer's disease. This review highlights current evidence for the expression of peripheral nAChRs in cells other than neurons and how they participate in fundamental processes, such as inflammation. Understanding these processes may offer novel therapeutic strategies to approach inflammatory diseases, as well as precautions in the design of interventional drugs.     

Prolonged nicotine exposure does not alter GABA(B) receptor-mediated regulation of brain reward function

Gamma-aminobutyric acid subtype B (GABA(B)) receptors play an important role in regulating brain reward function. Accumulating evidence suggests that chronic exposure to drugs of abuse may alter GABA(B) receptor function. The present studies investigated whether chronic nicotine administration, using a regimen that induces nicotine dependence, increased inhibitory regulation of brain reward function by GABA(B) receptors, as measured by intracranial self-stimulation (ICSS) thresholds in rats. Such an action of nicotine may contribute to the reward deficit observed during nicotine withdrawal. Nicotine-dependent and control rats received the GABA transaminase inhibitor gamma-vinyl-GABA or the GABA(B) receptor agonist CGP44532 according to a within-subjects Latin square design, and ICSS thresholds were assessed post-injection. Systemic administration of the lowest doses of GVG or CGP44532 did not alter reward thresholds in control or nicotine-treated rats, whereas the highest doses of each drug elevated thresholds similarly in both groups. Further, micro-infusion of CGP44532 directly into the ventral tegmental area elevated ICSS thresholds similarly in saline- and nicotine-treated rats. Overall, these data demonstrate that prolonged nicotine exposure did not alter GABA(B) receptor-mediated regulation of brain reward function, and suggest that alterations in GABA(B) receptor activity are unlikely to play a role in the brain reward deficits associated with spontaneous nicotine withdrawal.     

The appetite-suppressant effect of nicotine is enhanced by caffeine

AIM: To test whether the anorectic effect of nicotine may be amplified by caffeine. METHODS: Chewing gums with nicotine and caffeine were administered to 12 healthy young men of normal weight. Different combinations of 0, 1 or 2 mg of nicotine and 0, 50 or 100 mg of caffeine were applied during a 2-h period in a randomized, double blind, cross over design. Appetite sensations were measured using visual analogue scales. RESULTS: Hunger and prospective food consumption were negatively associated with the increasing doses of nicotine, whereas satiety and fullness were positively associated with the increasing doses of nicotine (p < 0.05). Caffeine appeared to amplify the effects of nicotine on hunger and fullness as a caffeine x nicotine x time interaction was observed in these scores (p < 0.05). The 2-mg dose of nicotine in combination with the 100-mg dose of caffeine caused nausea in four of the non-smokers. However, the effects of nicotine and the caffeine x nicotine x time interaction persisted after the exclusion of these subjects. CONCLUSION: Caffeine added to nicotine chewing gum appears to amplify its attenuating effects on appetite and the combinations of 1-mg of nicotine with caffeine seem to be well tolerated.