Differential behavioral and neuroendocrine effects of repeated nicotine in adolescent and adult rats

Despite the high prevalence of tobacco abuse among adolescents, the neurobiology of nicotine addiction has been studied mainly in adult animals. Repeated administration of this drug to adult rats induces behavioral sensitization. Nicotine activates the HPA axis in adult rats as measured by drug-induced increases in ACTH and corticosterone. Both behavioral sensitization and corticosterone are implicated in drug addiction. We examined the expression of behavioral sensitization induced by nicotine as well as the changes in corticosterone levels after repeated injections of nicotine in adolescent and adult animals. Adolescent and adult rats received subcutaneous (s.c.) injections of saline or 0.4 mg/kg of nicotine once daily for 7 days. Three days after the last injection animals were challenged with saline or nicotine (0.4 mg/kg; s.c.). 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. Adult, but not adolescent, rats expressed behavioral sensitization. Pretreatment with nicotine abolished corticosterone-activating effect of this drug only in adult animals, indicating the development of tolerance at this age. Our results provide evidence that adolescent rats exposed to repeated nicotine display behavioral and neuroendocrine adaptations distinct from that observed in adult animals. (c) 2004 Elsevier B.V. All rights reserved.

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.

Bases neurofisiológicas da dependência do tabaco

A maioria dos estudos pré-clínicos e clínicos aponta a nicotina como o principal agente responsável pelo desenvolvimento da dependência ao tabaco. Muitos trabalhos têm demonstrado que as bases neurais da dependência à nicotina são semelhantes àquelas das outras drogas de abuso. A nicotina induz preferência condicionada por lugar e auto-administração e, portanto, atua como reforçador positivo, esse efeito parece ser mediado pelo sistema dopaminérgico mesolímbico. A nicotina também induz à sensibilização comportamental que é provavelmente resultante de alterações da expressão gênica do núcleo acumbens induzidas pela exposição prolongada a essa substância. A suspensão do uso de nicotina resulta em síndrome de abstinência. As evidências indicam que esses sinais e sintomas sejam mediados por receptores colinérgicos nicotínicos centrais e periféricos. Outros neurotransmissores, como por exemplo a serotonina e os peptídeos opióides, também podem estar envolvidos na mediação da dependência e síndrome de abstinência à nicotina. A revisão da literatura mostra a complexidade dos efeitos da nicotina no organismo. A integração entre as abordagens comportamental, neuroquímica e molecular possibilitará a compreensão dos mecanismos neurais da dependência ao tabaco e fornecerá as bases para o desenvolvimento racional de agentes terapêuticos que possam ser utilizados para o tratamento da dependência e síndrome de abstinência ao tabaco.

Métodos para abandono do tabagismo e tratamento da dependência da nicotina

O tabagismo está relacionado a 30% das mortes por câncer. É fator de risco para desenvolver carcinomas do aparelho respiratório, esôfago, estômago, pâncreas, cérvix uterina, rim e bexiga. A nicotina induz tolerância e dependência pela ação nas vias dopaminérgicas centrais, levando às sensações de prazer e recompensa mediadas pelo sistema límbico. É estimulante do sistema nervoso central (SNC), aumenta o estado de alerta e reduz o apetite. A diminuição de 50% no consumo da nicotina pode desencadear sintomas de abstinência nos indivíduos dependentes: ansiedade, irritabilidade, distúrbios do sono, aumento do apetite, alterações cognitivas e fissura pelo cigarro. O aconselhamento médico é fundamental para o sucesso no abandono do fumo. A farmacoterapia da dependência de nicotina divide-se em: primeira linha (bupropiona e terapia de reposição da nicotina), e segunda linha (clonidina e nortriptilina). A bupropiona é um antidepressivo não-tricíclico que age inibindo a recaptação de dopamina, cujas contra-indicações são: epilepsia, distúrbios alimentares, hipertensão arterial não-controlada, abstinência recente do álcool e uso de inibidores da monoaminoxidase (MAO). A terapia de reposição de nicotina pode ser feita com adesivos e gomas de mascar. Os efeitos da acupuntura no abandono do fumo ainda não estão completamente esclarecidos. As estratégias de interrupção abrupta ou redução gradual do fumo têm a mesma probabilidade de sucesso.

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

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

Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Exposure to acute restraint stress reinstates nicotine-induced place preference in rats

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)

Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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)

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.