Nicotina e adolescência: efeitos comportamentais em camundongos Suíços do tratamento farmacológico para a dependência

• Autor(a) principal: Claudio Neto, Sylvio
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12670
• topic: Adolescence; Nicotine; Treatment; Anxiety; Locomotor activity; Adolescência; Nicotina; Tratamento; Ansiedade; Atividade locomotora; Nicotina; Adolescentes; Ansiedade na adolescência; Camundongo como animal de laboratório; Transtorno por uso de tabaco; CNPQ::CIENCIAS DA SAUDE

Nicotine is the main pharmacologically active substance in cigarettes responsible for dependency. It has been shown that teenagers that are exposed to nicotine, have increased risks of acquiring long lasting dependence. Strategies to facilitate the interruption of nicotine use have been developed, but little is known about the effects of nicotine exposure during adolescence and even less of the short and long-term effects of the treatments available for the reversal of the dependency. The objective of this work was to analyze behavior, in the Elevated Plus Maze test (LCE) and in the Open Field test (CA), of mice exposed to nicotine during adolescence and then treated with bupropion or varenicline. From post-natal day 30 (PN30) to PN45, 899 male Swiss mice were exposed to a 2% saccharine solution containing 50 µg/ml of nicotine (NIC) or to a 2% saccharine solution (SAC) in standard plastic bottles. From PN46 to PN56, the animals were treated orally (gavage) with one of the following drugs: a) 0.1 mg/kg varenicline (VAR1); b) 1.0 mg/kg varenicline (VAR2); c) 30 mg/kg bupropion (BUP1); d) 60 mg/kg bupropion (BUP2). In addition to the above treatments, two other treatments were performed: a) animals received nicotine (NIC) in accordance with the method used during the exposure period, receiving additionally vehicle solution by gavage; b) animals receiving nicotine (NIC) and who received, by gavage, VAR1. The following experimental groups were then formed (exposure-treatment): 1) SAC-VEH; 2) SAC-NIC; 3) SAC-VAR1; 4) SAC-VAR2; 5) SAC-NICVAR1; 6) SAC-BUP1; 7) SAC-BUP2; 8) NIC-VEH; 9) NIC-NIC; 10) NIC-VAR1; 11) NIC-VAR2; 12) NIC-NICVAR1; 13) NIC-BUP1; 14) NIC-BUP2. The animals were behaviorally tested in one of three different periods: a) During treatment (LCE in PN54 and CA in PN55); (b) with 5 days of termination of treatment (LCE in PN61 and CA in PN62); c) with 10 days of termination of treatment (LCE in PN66 and CA in PN67). Different animals were used in each period. Regarding the LCE, our main findings indicate that, during treatment, bupropion partially reversed the ansiogenic effect of the exposure to nicotine, while varenicline did not present a consistent improvement in the results. With 5 days of termination, no effects on anxiety associated with bupropion were observed, but the combined treatment of nicotine with varenicline was markedly anxiolytic. With 10 days of termination, the lower dose of bupropion normalized the levels of anxiety-like behavior. In this same period, the combined treatment with varenicline and nicotine normalized the anxiolytic behavior from exposure to nicotine, while treatment only with varenicline (either dose) presented an anxiolytic effect. No effects of exposure or treatment were observed on the locomotor activity. Our results suggest that treatment with bupropion and varenicline, in combination or not with nicotine, have a safe profile for use during adolescence.