Prior exposure to stress delays extinction but does not modify reinstatement of nicotine-induced conditioned place preference

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of chronic stress on nicotine-induced locomotor activity and corticosterone release in adult and adolescent rats

We examined nicotine-induced locomotion and increase in corticosterone plasma levels in adolescent and adult animals exposed to chronic restraint stress. Adolescent [postnatal day (P) 28-37] and adult (P60-67) rats were restrained for 2 hours once daily for 7 days. Three days after the last exposure to stress, the animals were challenged with saline or nicotine (0.4 mg/kg subcutaneously). Nicotine-induced locomotion was recorded in an activity cage. Trunk blood samples were collected in a subset of adolescent and adult rats and plasma corticosterone levels were determined by radioimmunoassay. Exposure to stress did not affect the nicotine-induced locomotor- or corticosterone-activating effects in both ages.

Amphetamine- and nicotine-induced cross-sensitization in adolescent rats persists until adulthood

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stress induces behavioral sensitization, increases nicotine-seeking behavior and leads to a decrease of CREB in the nucleus accumbens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Action of nicotine and ovariectomy on bone regeneration after tooth extraction in rats

Purpose: The purpose of this study was to evaluate the effects of nicotine and ovariectomy on alveolar bone regeneration after exodontias in rats.Materials and Methods: For 30 days, sham ovariectomized (OVX)/NaCl, sham OVX/nicotine, OVX/NaCl, and OVX/nicotine animals were given 2 daily injections of saline or hemisulfate of nicotine. After this period, exodontic procedures were carried out and treatment continued up to the time of euthanasia on clays 7 and 14 when the alveoli were removed for further analyses.Results: The data confirmed that nicotine significantly delays the alveolar regeneration process after dental extraction in rats and showed that the association of nicotine with ovariectomy exacerbates these results.Conclusion: These results indicate that nicotine potentiated the effect of estrogen deficiency on bone regeneration induced by ovariectomy. (c) 2010 American Association of Oral and Maxillofacial Surgeons Oral Maxillofac Surg 68:2675-2681, 2010

Nicotine-Induced Damage Affects Gingival Fibroblasts in the Gingival Tissue of Rats

Background: Very limited information is available from in vivo studies about whether smoking and/or nicotine affect gingival tissues in the absence of plaque. The purpose of this study is to evaluate the effect of the systemic administration of nicotine in the proliferation and counting of fibroblast-like cells in the gingival tissue of rats.Methods: Thirty adult male Wistar rats were randomly assigned into two groups to receive subcutaneous injections of a saline solution (control group = group C) or nicotine solution (group N; 3 mg/kg) twice a day. The animals were euthanized 37, 44, or 51 days after the first subcutaneous injection. Specimens were routinely processed for serial histologic sections. Five fields of view in the connective tissue adjacent to the gingival epithelium and above the alveolar bone crest of the maxillary first molar were selected for the counting of fibroblast-like cells. Data were statistically analyzed (P<0.05).Results: The intergroup analysis detected a lower number of fibroblast-like cells in group N compared to group C on days 37 (2.65 +/- 1.41 and 6.67 +/- 3.25, respectively), 44 (2.70 +/- 1.84 and 8.57 +/- 2.37, respectively), and 51(2.09 +/- 1.41 and 7.49 +/- 2.60, respectively) (P<0.05). The quantification of fibroblast-like cells showed no significant difference (P >0.05) in the intragroup analysis of control and nicotine throughout experimental periods. In the intergroup analysis, group N had reduced proliferating cell nuclear antigen positive fibroblasts compared to group C in all periods (P<0.05).Conclusion: The daily systemic administration of nicotine negatively affected, in vivo, the number and proliferation of fibroblast-like cells in the gingival tissue of rats. J Periodontol 2011;82:1206-1211.

Influence of low-level laser therapy on wound healing in nicotine-treated animals

Low-level laser therapy (LLLT) has been shown to have several biological effects that favor the healing process, and nicotine has been shown to delay the healing process. In this study we investigated the healing of open wounds created on the back of rats treated with nicotine with or without LLLT. of 115 animals, 59 received subcutaneous injections of saline solution, and the others received subcutaneous injections of nicotine (3 mg/kg body weight), twice a day throughout the study period. After 30 days, skin wounds were created on the back of the animals. The animals receiving saline injections were divided into two groups: group 1 (G1, n = 29), in which the wounds were left untreated, and group 2 (G2, n = 30), in which the wounds were treated with LLLT (GaAlAs, 660 nm, 30 mW, 5.57 J/cm(2) per point, 0.39 J, 13 s per point, 0.42 W/cm(2)). The animals receiving nicotine injections were also divided into two groups: group 3 (G3, n = 29), in which the wounds were left untreated, and group 4 (G4, n = 27), in which the wounds were treated with LLLT. The animals were killed 3, 7 or 14 days after surgery. Wound healing was evaluated histologically both qualitatively and semiquantitatively. Wounds of G2 showed a delay in epithelial migration and connective tissue organization compared to those of G1. Wounds of G2 showed faster healing than those of G1; similarly, wounds of G4 showed more advanced healing than those of G3. LLLT acted as a biostimulatory coadjuvant agent balancing the undesirable effects of nicotine on wound tissue healing.

Treatment of experimental periodontal disease with antimicrobial photodynamic therapy in nicotine-modified rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphological alterations in the epithelium of the oral mucosa of rats (Rattus norvegicus) submitted to long-term systemic nicotine treatment

Smoking is considered to be the most albeit preventable cause of diseases and premature deaths in the history of mankind. The local action of tobacco on the oral mucosa can cause precancerous and cancerous lesions. However, there is not enough evidence to establish all the systemic effects caused by nicotine on the organism. Thus, the aim of the present study was to characterize the cellular changes of the cheek mucosa of rats submitted to long-term systemic nicotine treatment. Twenty male rats were divided into two experimental groups: a nicotine group and a control group, each consisting of 10 animals. The nicotine group was injected daily with 0.250 mg of nicotine per 100 g of body weight. All animals received a solid diet and water ad libitum. After 90 days of treatment, all animals were weighed and sacrificed. Samples of cheek mucosa were collected for light and transmission electron microscopy. The results revealed oral epithelium containing atypical cells that were characterized by atrophy, cell membrane disorganization and tissue damage. It was concluded that systemic administration of nicotine damaged the cellular integrity of the oral mucosa, impairing tissue function and predisposing the tissue to the action of different pathogenic agents and also to that of other carcinogenic substances present in tobacco. (c) 2006 Elsevier Ltd. All rights reserved.

Morphometric and ultrastructure features of the ventral prostate of rats (Rattus norvegicus) submitted to long-term nicotine treatment

The harmful effects of nicotine on male genital system fertility have been reported in experimental and clinical studies. However, its effects on prostatic cells and glandular pathogenesis remain unclear. The aim of the present study was to analyse the histological, histochemical and ultrastructural alterations, in addition to stereology, of the ventral lobe of the prostate of rats, submitted to chronic nicotine administration, as well as to establish the relationship between these changes and prostate diseases. Twelve male Wistar rats (Rattus norvegicus) were divided into two experimental groups: group I (nicotine) and group II (control). Samples of the ventral prostate were collected, processed and submitted to histological analysis, acid phosphatase histochemistry and ultrastructural analysis by transmission and scanning electron microscopies. The results showed that in the nicotine group, the secretory epithelial cells of the ventral lobe of the prostate were atrophied, and prostatic intraepithelial neoplasia occurred and reduced the expression of acid phosphatase. The disorganisation of organelles involved in the glandular secretory process, accompanied by biomembrane destructuring, was also observed. In conclusion, nicotine causes drastic alterations in the secretory epithelium of the ventral prostate, compromising its function. Furthermore, nicotine also induces premalignant lesions in the prostate gland, thus representing a risk factor in the development of prostate diseases.

Recent developments for smoking cessation and treatment of nicotine dependence

Nicotine is an addictive drug like heroin, amphetamine or cocaine. Addiction to tobacco leads to significant failure rates in programmes for smoking cessation. The alpha(4)beta(2) and alpha(7) nicotinic acetylcholine receptors (nAChRs) and CB1 cannabinoid receptors play an important role in nicotine addiction.

Root surface conditioning with nicotine or cotinine reduces viability and density of fibroblasts in vitro

The purpose of study was to evaluate fibroblast attachment and cellular morphology on root surfaces chemically conditioned with nicotine or cotinine. A secondary objective was to determine if mechanical scaling and root planning of these chemically conditioned surfaces would alter cellular attachment. Root surface dentin specimens were prepared from uniradicular teeth of non-smoking patients. Specimens were randomly assigned to two experimental groups: no treatment (chemical conditioning only) and scaling and root planning after conditioning (SRPC). The concentrations of the tested substances were in the range of 0-1 mg/mL (nicotine) and 0-1 ?g/mL (cotinine). After a 24-h conditioning period, dentin slices were incubated with continuous lineage of fibroblastic cells from rat (McCoy cells) for another 24 h. Specimens were prepared for SEM analysis and microphotographs. The statistical analysis of the data indicated significant alteration of cellular morphology on fibroblasts that were grown on root surface exposed to nicotine concentrations greater than 1 ? g/mL. This effect of nicotine was not reduced by SRPC. on the other hand, in the SRPC group cellular density was greater. For cotinine-conditioned specimens, the greater concentrations also led to alteration on morphology, and these alterations were observed in the SRPC group as well. Cotinine did not induce significant changes on cellular density. The results indicated that fibroblasts are negatively influenced by nicotine present on the dentin substrate and also that scaling may reduce these effects. Cotinine treatment on root surfaces may alter cell morphology and density but these effects were less severe than that promoted by nicotine, and were not affected by scaling.

Enhanced nicotine-seeking behavior following pre-exposure to repeated cocaine is accompanied by changes in BDNF in the nucleus accumbens of rats

We investigated the behavioral and molecular interactions between cocaine and nicotine, through evaluating locomotor activity, nicotine intravenous self-administration and gene expression. Locomotor sensitization was induced in male Wistar rats by repeated cocaine (20 mg/kg; i.p.) or saline injections once a day over 7 days. Three days after the last injection, rats were challenged with either saline or cocaine (15 mg/kg; i.p.) and the locomotor activity was measured. The very next day animals received either saline or nicotine (0.4 mg/kg; s.c.) and the locomotor cross-sensitization was tested. Animals were then prepared with intrajugular catheters for nicotine self-administration. Nicotine self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement and a 24-h unlimited access binge. Immediately after the binge sessions animals were decapitated, the brains were removed and the nucleus accumbens was dissected. The dynorphin (DYN), μ-opioid receptor (mu opioid), neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), tropomyosin-related tyrosine kinase B receptor (TrkB) and corticotropin- releasing factor receptor type 1 (CRF-R1) gene expression were measured by the reverse transcription-polymerase chain reaction (RT-PCR). Pretreatment with cocaine caused sensitization of cocaine motor response and locomotor cross-sensitization with nicotine. In the self-administration experiments repeated cocaine administration caused an increase in the nicotine break point and nicotine intake during a 24 h binge session. © 2013 Elsevier Inc.

Influence of nicotine and cotinine impregnation on the first step of periodontal regeneration: clot stabilization

This study analyzes the clot stabilization on root surfaces of teeth impregnated with cotinine and nicotine and the influence of the scaling in the adhesion of blood components, observing the influence of new exposition to nicotine and/or cotinine after scaling. Fifteen human teeth extracted due to periodontal disease of non-smokers patients were selected and manually scaled. Four dentin blocks were obtained from each tooth (n = 60). Samples received blood application or reimpregnation with nicotine and/or cotinine, depending on the groups. Group 1: PBS immersion + root scaling + blood; group 2: nicotine + root scaling + blood; group 3: nicotine + root scaling + nicotine reapplication + blood; group 4: cotinine + root scaling + blood; group 5: cotinine + root scaling + cotinine reapplication+ blood; group 6: nicotine and cotinine + root scaling + nicotine and cotinine + blood. Samples were kept in 2 ml of each substance for 24 hours. Each group received a blood drop and was analyzed by SEM. The higher amount of blood components was present in teeth exposed to cotinine and the groups submitted to scaling and blood application in comparison with groups that received reapplication of toxic substances after scaling. The greater toxic effect on root dentin surface was after the exposure to nicotine and cotinine. Results suggest that periodontal healing may be delayed in smokers due to the direct inhibition of clot stabilization on the root surface when nicotine and cotinine are present concomitantly.