Efeitos comportamentais e endócrinos do tratamento com a vareniclina em um modelo experimental de exposição à nicotina durante a adolescência

• Ano de defesa: 2012
• Autor(a) principal: Garrão, Natalie Razuck
• Orientador(a): Bastos, Alex Cardoso
• Banca de defesa: Filgueiras, Cláudio Carneiro , Oliveira, Elaine de , Carvalho, Anderson Ribeiro
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Fisiopatologia Clínica e Experimental
• Departamento: Centro Biomédico::Faculdade de Ciências Médicas
• País: BR
• Palavras-chave em Português: Nicotina; Desenvolvimento; Vareniclina; Adolescência; Comportamento; Sistema endócrino; Fumo; Cigarro; Receptivos nicotínicos
• Palavras-chave em Inglês: Nicotine; Development; Varenicline; Adolescence; Behavior; Endocrine system
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::NEUROFISIOLOGIA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/12775

Nicotine is considered the main psicoactive component of tobacco and it induce its central pharmacological effects by acting on cholinergic nicotinic receptors (nAChRs). The maturation of the cholinergic system is consolidated during the periadolescent period, which suggests that the adolescent brain is vulnerable to the effects of cholinergic stimulants. Considering the deleterious effects of tobacco consumption, including addiction, several therapeutic strategies are being developed to aid in the interruption of consumption. Varenicline treatment, a partial agonist of the α4β2 nAChRs is one of the most recent ones. Little is known regarding the effects of nicotine exposure during adolescence and even less is known regarding the short and long term effects of the available treatments for addiction during this period. In this sense, the aim of the present work is to study the behaviors associated with anxiety and novelty seeking, as well as adrenal function, in animals exposed to nicotine during adolescence and subsequently treated with a procedure to cure addiction to nicotine. This study used 150 adolescent Swiss mice of both sexes. The animals were exposed (orally) to a nicotine (50µg/ml - NIC) solution or to a saccharine (2% - SAC) solution from the 30th postnatal day (PN) to PN45 and then treated by gavage with one of the following substances from PN45 to PN56: 1) vareniclina (0.1 or 1.0 mg/kg/day - VAR1 and VAR2 respectively); 2) vehicle (VEH); 3) nicotine (using the dose previously used from PN30 to PN45 - NIC). Seven experimental groups were used: SACVEH, SACVAR1, SACVAR2, NICVEH, NICVAR1, NICVAR2 and NICNIC. On PN55, the animals were tested in the elevated plus maze (EPM) for 5 min and, 2 h later, they were tested for 5 min on the hole board arena (HB). The tissue samples collected on PN56 (after the animals sacrifice) were: left adrenal gland for the analysis of catecholamine content; right adrenal gland for the analysis of tyrosine hidroxilase expression; serum for the analysis of corticosterone concentration. Our results show that by the end of the treatment no differences were observed between groups regarding behaviors associated with anxiety in the EPM and those associated with novelty-seeking in the HB. Conversely, the analysis of the number of explored holes on the center of the HB, also used as a measure of anxiety, suggest that varenicline by itself and the continued exposure to nicotine are anxiogenic but that varenicline treatment following nicotine exposure keeps results within normal levels. Regarding the endocrine system, the catecholamine adrenal content was corrected by varenicline treatment, the serum corticosterone levels were increased by nicotine exposure and the tyrosine hidroxilase expression was increased by varenicline treatment. Our study indicates that, by the end of the treatment, behavioral as well as endocrine parameters were affected in our model of nicotine exposure during adolescence and subsequent varenicline treatment. Further studies will have to address this parameters in later periods with then aim of verifying whether the observed alterations persist up to adulthood.