Efeitos somáticos e comportamentais do uso da vareniclina em um modelo animal de exposição à fumaça do cigarro durante a adolescência

Abstract

Tobacco is the second most consumed psychoactive substance in the world, being considered a threat to public health due to its potential harm. Mostly, the habit of smoking is established during adolescence and extends into adulthood. The use of tobacco products during this period of development generates nicotine dependence quickly and there is greater difficulty in maintaining abstemiousness when trying to stop use. Despite the considerable damage resulting from the early initiation of cigarette consumption by adolescents, little is known, in this age group, about the impact of the main therapeutic alternatives involving drugs that are already available for adults. Varenicline, a partial α4β2 and total α7 nicotinic cholinergic receptor agonist, is one of the drugs approved for the treatment of nicotine-associated substance use disorder in adults. In the present study, this substance was used in the treatment of an animal model of exposure to cigarette smoke during adolescence with the aim of evaluating its effects on somatic and behavioral parameters. From postnatal day 30 (PN30) to 45, 384 Swiss mice (both sexes) were exposed to cigarette smoke (0.73 mg nicotine; FUM) or air (AR) for 8 h/day in automated exposure. At PN41, treatment with varenicline (0.5 mg/kg/bid v.o.; VAR) or water (AG) was initiated; from PN46 to PN56, the dose was doubled. Half of the animals were tested in the Elevated Plus Maze (EPM) and in Hole Board (HB) during treatment (PN54/PN55; treatment) and half 30 days later (PN84/PN85; withdrawal). It was observed that the smoke reduced liquid intake, feed consumption and body mass during exposure. During the treatment period, FUM males showed an increase in behaviors associated with anxiety in the EPM when compared to AR males. Still in the EPM, the treatment with varenicline was able to normalize the locomotor activity of males, which had been reduced by the smoke. In the HB, both FUM females and males showed a reduction in the behavior associated with novelty seeking when compared to AR animals. Still in the HB, varenicline normalized, in females, the increase in behaviors associated with anxiety caused by exposure to smoke. During withdrawal, a reduction in anxious-like behavior was observed in VAR females in the EPM, which was corroborated by the data obtained in the HB. In males, varenicline treatment partially reversed the smoke-induced reduction in the expression of anxiety-associated behaviors. In general, treatment with varenicline did not affect in a deleterious way the variables associated with anxiety-like and novelty-seeking behaviors, having been able to reverse, totally or partially, the deleterious effects of exposure to cigarette smoke on several variables. This pattern of results suggests that the use of varenicline is safe in adolescents who want to stop smoking